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Publication : Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal γδ T cells.

First Author  Dupraz L Year  2021
Journal  Cell Rep Volume  36
Issue  1 Pages  109332
PubMed ID  34233192 Mgi Jnum  J:317575
Mgi Id  MGI:6856532 Doi  10.1016/j.celrep.2021.109332
Citation  Dupraz L, et al. (2021) Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal gammadelta T cells. Cell Rep 36(1):109332
abstractText  Gut interleukin-17A (IL-17)-producing gammadelta 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 gammadelta 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 gammadelta T cells. Propionate acts directly on gammadelta 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 gammadelta 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 gammadelta T cell functions and offer therapeutic perspectives of these cells.
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