Dietary cysteine enhances intestinal stemness via CD8 T cell-derived IL-22.

bioRxiv : the preprint server for biology
Authors
Abstract

A critical question in physiology is understanding how tissues adapt and alter their cellular composition in response to dietary cues. The mammalian small intestine, a vital digestive organ that absorbs nutrients, is maintained by rapidly renewing Lgr5 intestinal stem cells (ISCs) at the intestinal crypt base. While Lgr5 ISCs drive intestinal adaptation by altering self-renewal and differentiation divisions in response to diverse diets such as high-fat diets and fasting regimens, little is known about how micronutrients, particularly amino acids, instruct Lgr5 ISC fate decisions to control intestinal homeostasis and repair after injury. Here, we demonstrate that cysteine, an essential amino acid, enhances the ability of Lgr5 ISCs to repair intestinal injury. Mechanistically, the effects of cysteine on ISC-driven repair are mediated by elevated IL-22 from intraepithelial CD8αβ T cells. These findings highlight how coupled cysteine metabolism between ISCs and CD8 T cells augments intestinal stemness, providing a dietary approach that exploits ISC and immune cell crosstalk for ameliorating intestinal damage.

Year of Publication
2025
Journal
bioRxiv : the preprint server for biology
Date Published
02/2025
ISSN
2692-8205
DOI
10.1101/2025.02.15.638423
PubMed ID
39990373
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