Mingming Sun 1 , 2 , Wei Wu 1 , 2 , Liang Chen 1 , 2 , Wenjing Yang 1 , 2 , Xiangsheng Huang 2 , Caiyun Ma 1 , Feidi Chen 3 , Yi Xiao 2 , Ye Zhao 2 , Chunyan Ma 2 , Suxia Yao 2 , Victor H. Carpio 4 , Sara M. Dann 4 , Qihong Zhao 5 , Zhanju Liu , 1 , Yingzi Cong , 2 , 3
3 September 2018
T-cells are crucial in maintanence of intestinal homeostasis, however, it is still unclear how microbiota metabolites regulate T-effector cells. Here we show gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43). Microbiota antigen-specific Gpr43 −/− CBir1 transgenic (Tg) Th1 cells, specific for microbiota antigen CBir1 flagellin, induce more severe colitis compared with wide type (WT) CBir1 Tg Th1 cells in Rag −/− recipient mice. Treatment with SCFAs limits colitis induction by promoting IL-10 production, and administration of anti-IL-10R antibody promotes colitis development. Mechanistically, SCFAs activate Th1 cell STAT3 and mTOR, and consequently upregulate transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1), which mediates SCFA-induction of IL-10. SCFA-treated Blimp1 −/− Th1 cells produce less IL-10 and induce more severe colitis compared to SCFA-treated WT Th1 cells. Our studies, thus, provide insight into how microbiota metabolites regulate Th1 cell functions to maintain intestinal homeostasis.
T cells play a critical role in intestinal homeostasis, with increasing evidence suggesting a role for the microbiome metabolome in modulating this response. Here the authors show short-chain fatty acids promote IL-10 production in Th1 cells.