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.
Gut microbiota-derived metabolites, particularly propionate, act directly on γδ T cells to inhibit IL-17 production in a histone deacetylase-dependent manner