/ en /news/new-dictionary-immune-responses-reveals-far-more-complexity-immune-system-previously-thought <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Wed, 06 Dec 2023 16:00:00 +0000 adicorat 5556171 at /news/exploring-autoimmunitys-regulatory-roots <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Fri, 06 May 2022 13:30:21 +0000 tulrich@broadinstitute.org 1131936 at /news/researchers-discover-immune-cell-%E2%80%9Chubs%E2%80%9D-hiding-tumors <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Tue, 31 Aug 2021 14:10:29 +0000 Corie Lok 1073766 at /news/researchers-identify-protein-%E2%80%9Csignature%E2%80%9D-severe-covid-19 <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Tue, 04 May 2021 15:17:25 +0000 tulrich@broadinstitute.org 867126 at /news/how-scientists-launched-study-days-probe-covid-19%E2%80%99s-unpredictability <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Thu, 29 Oct 2020 19:48:46 +0000 leah@broadinstitute.org 671841 at /news/research-roundup-july-31-2020 <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Fri, 31 Jul 2020 15:36:28 +0000 Namrata Sengupta 635586 at /coronavirus/epidemiology-surveillance <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Tue, 21 Apr 2020 20:20:36 +0000 admin 628241 at /news/new-tool-could-help-researchers-design-better-cancer-vaccines <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Mon, 16 Dec 2019 05:00:00 +0000 Corie Lok 626281 at /news/chemical-approach-imaging-cells-inside <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Thu, 20 Jun 2019 15:55:38 +0000 kzusi@broadinstitute.org 549266 at /news/research-roundup-february-1-2019 <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" class="datetime">December 6, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>New “dictionary” of immune responses reveals far more complexity in the immune system than previously thought</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists map the effects of 86 immune-signaling molecules called cytokines on every major immune cell type, creating a reference for studying the inner workings of the immune system.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:00:00-05:00" title="Wednesday, December 6, 2023 - 11:00" class="datetime">December 6, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=RoMWMuSd 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=hTTjkvxK 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=Jp2vNcjV 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=3Olv4jre 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/1223%20QA%20Headshots-01.png?h=ae0fde30&amp;itok=qqN3pgnO" alt="Portraits of Ang Cui and Nir Hacohen." title="Portraits of Ang Cui and Nir Hacohen." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Len Rubenstein (right photo) </div> <div class="media-caption__description"> Ang Cui (left) and Nir Hacohen (right). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/699/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/699/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/699/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The immune system can carry out many biological processes, from killing viruses to fighting cancer, thanks in large part to approximately 100 key cell-signaling proteins called cytokines, which instruct immune cells what to do. Cytokines are also targeted by drugs for many diseases such as rheumatoid arthritis, COVID-19, and cancer, but until now, scientists haven’t had a comprehensive view of how different immune cells respond to different cytokines because the immune system is so complex.</p> <p>A new, large-scale reference created by researchers at the ӳ����ý of MIT and Harvard could help scientists and clinicians better understand the role of cytokines in health and disease. The reference, called the <a href="http://www.immune-dictionary.org/" target="_blank">Immune Dictionary</a>, appears today in <em><a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Nature</a></em>.</p> <p>Using single-cell RNA sequencing to analyze gene expression in individual cells, the researchers have found how 86 major cytokines affect 17 immune cell types in mice. They found a surprising level of complexity in the immune system: Cytokines can trigger more immune responses, and immune cells can perform more functions than previously thought.</p> <p>The team also developed software for scientists, called Immune Response Enrichment Analysis (IREA), that they can use to identify the most active cytokines involved in a disease or drug response, and how different immune cells carry out different functions depending on which cytokine signal they receive.&nbsp;</p> <p>We spoke with <a href="https://connects.catalyst.harvard.edu/Profiles/display/Person/211262" target="_blank">Ang Cui</a>, first and co-corresponding author on the study, formerly a postdoctoral researcher in <a href="/node/4724">Nir Hacohen</a>’s lab at ӳ����ý and now an assistant professor at the Harvard School of Dental Medicine and Harvard Medical School (HMS); and Hacohen, a co-corresponding author, institute member at the ӳ����ý, and professor of medicine at HMS and Massachusetts General Hospital; about what makes their immune dictionary unique and how it could impact immunology research in this Q&amp;A.&nbsp;</p> <p><strong>What makes this study significant?</strong></p> <p><strong>NH:</strong> This is the first single-cell resolution dictionary of each major immune cell type responding to each major cytokine <em>in vivo</em> at an unprecedented scale. Typical studies of immune responses may look at roughly five immune cell types in a couple of conditions, whereas this study looked at nearly all major immune cell types responding to nearly all of the major cytokines. That’s more than 1,400 cytokine-cell type combinations — two orders of magnitude larger than typical studies, allowing the team to comprehensively document the complexity of the immune system.&nbsp;</p> <p>The scale was unique, but also, doing this at single-cell resolution was critical because it turns out that if you isolate a macrophage, there are actually different types of monocytes and macrophages. Single-cell resolution allows for a more natural view of those subsets. We also made the decision to do this in the mouse rather than in culture. There have been a lot of papers over the years where people take cells and stimulate them with cytokines in dishes in the lab, but we never knew what it meant in an animal. This was the first time we've done it in a physiological context.&nbsp;</p> <p><strong>AC:</strong> This research could have far-reaching implications, accelerating our understanding of natural immune responses and human immune-related diseases. For many immune-mediated diseases, there's no cure or treatment. Some patients develop resistance to treatment and we cannot predict who they will be. There are many open questions, and having this foundational reference can significantly improve our understanding of the immune system. In the future, when doctors give patients cytokine therapies targeting the immune system, they could potentially look in the Immune Dictionary for expected cell-level immune responses.&nbsp;</p> <p><strong>Did any results surprise you?</strong></p> <p><strong>AC:</strong> We found that both the immune responses to cytokines and the plasticity of immune cells were much more complex than we previously appreciated. Even IL-1β, one of the first discovered and most well-studied cytokines, induces much more complex responses than previously known. IL-1β can induce distinct responses in each cell type, which shows how a single cytokine can trigger a coordinated, multicellular immune response. This could only have been revealed by creating this kind of global map of every immune cell response to the cytokine.</p> <p><strong>NH:</strong> The dictionary gave us many surprises. I was shocked by what we found about IL-1β. I think for many people, this will help them make sense of this central cytokine.</p> <p><strong>AC:</strong> The study also showed us how plastic immune cells are. For example, macrophages are well known to be polarized into M1-like (proinflammatory) or M2-like (reparative) states (which helps determine their function), but we didn’t know how other immune cell types are polarized. We found that every immune cell type can be polarized into diverse states depending on which cytokines they receive. Natural killer cells, for example, can perform different functions depending on which cytokines we give them.&nbsp;</p> <p><strong>How do you hope other scientists will use these findings?</strong></p> <p><strong>AC:</strong> Long-term, a more precise understanding of <em>in vivo</em> immune responses could enable precision medicine, overcoming current limitations for creating effective immunotherapies for a wide range of diseases. The dictionary could also be used for basic biology studies, if you want to know what cytokines can trigger a specific gene, for example. We’ve already used our software to interrogate the immune response in four diseases: lupus, cancer, COVID-19, and hepatitis C. It identified the most active cytokines for each disease.</p> <p><strong>NH:</strong> If I were an immunologist working on my single-cell dataset in any disease or in any process, I would want to run a cytokine analysis using this new reference, because cytokines drive so many of the decisions. I hope our approach helps scientists make sense of any immune process, vaccine, disease, or therapy response, so that one can infer which cytokines are contributing to it. You could then block those cytokines in animal models and see what their roles are. We're excited to see what people will do with it.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--image-with-caption image-with-caption"> <div class="image-with-caption__col"> <div class="image-with-caption__col-row"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-pt-image-with-caption"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_desktop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=0MJpJaOI 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="1256" height="689"> <source srcset="/files/styles/pt_image_with_caption_laptop/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=tPJyx61e 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="1221" height="584"> <source srcset="/files/styles/pt_image_with_caption_tablet/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=kMk_JmcF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="707" height="466"> <source srcset="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="329"> <img loading="eager" width="499" height="329" src="/files/styles/pt_image_with_caption_phone/public/immune%20dictionary.jpg?h=187f8ebb&amp;itok=LzBkVfQ_" alt="Graphic depicting variety of immune responses to cytokines" title="Graphic depicting variety of immune responses to cytokines" typeof="foaf:Image"> </picture> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institute of Health, Adelson Medical Research Foundation, Natural Sciences and Engineering Research Council of Canada, MIT Whitaker Health Sciences Fund, MIT Wellington and Irene Loh Fund, and MIT Undergraduate Research Opportunities Program.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Cui A et al. <a href="https://www.nature.com/articles/s41586-023-06816-9" target="_blank">Dictionary of immune responses to cytokines at single-cell resolution</a>. <em>Nature</em>. Online December 6, 2023. DOI:10.1038/s41586-023-06816-9.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cell-circuits" hreflang="en">Cell Circuits Program</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/rna-sequencing" hreflang="en">RNA sequencing</a></div> </div> </div> </div> </div> </div> Fri, 01 Feb 2019 15:49:02 +0000 tulrich@broadinstitute.org 447516 at