Journal
CELL REPORTS
Volume 36, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109332
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Funding
- Foundation for Medical Research
- Association Francois Aupetit
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The gut microbiota represses IL-17 production by gamma delta T cells through the production of metabolites, particularly propionate.
Gut interleukin-17A (IL-17)-producing gamma delta T cells are tissue-resident cells that are involved in both host defense and regulation of intestinal inflammation. However, factors that regulate their functions are poorly understood. In this study, we find that the gut microbiota represses IL-17 production by cecal gamma delta T cells. Treatment with vancomycin, a Gram-positive bacterium-targeting antibiotic, leads to decreased production of short-chain fatty acids (SCFAs) by the gut microbiota. Our data reveal that these microbiota-derived metabolites, particularly propionate, reduce IL-17 and IL-22 production by intestinal gamma delta T cells. Propionate acts directly on gamma delta T cells to inhibit their production of IL-17 in a histone deacetylase-dependent manner. Moreover, the production of IL-17 by human IL-17-producing gamma delta T cells from patients with inflammatory bowel disease (IBD) is regulated by propionate. These data contribute to a better understanding of the mechanisms regulating gut gamma delta T cell functions and offer therapeutic perspectives of these cells.
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