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

作者：Louise Dupraz, Aurélie Magniez, Nathalie Rolhion, Mathias L. Richard, Grégory Da Costa, Sothea Touch, Camille Mayeur, Julien Planchais, Allison Agus, Camille Danne, Chloé Michaudel, Madeleine Spatz, François Trottein, Philippe Langella, Harry Sokol, Marie‐Laure Michel · 发表于：Cell Reports · 年份：2021 · DOI：10.1016/j.celrep.2021.109332 · 被引用次数：277 · 研究领域：Immune Cell Function and Interaction、Gut microbiota and health、IL-33, ST2, and ILC Pathways

Gut interleukin-17A (IL-17)-producing γδ 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 γδ 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 γδ T cells. Propionate acts directly on γδ 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 γδ 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 γδ T cell functions and offer therapeutic perspectives of these cells.