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- W4313360052 abstract "Abstract The mechanisms by which gut microbiota regulate host immune responses are still not completely understood. Short chain fatty acids (SCFA), mainly acetate (C2), propionate (C3), and butyrate (C4), the metabolites produced solely by gut microbiota, have been shown to promote development of Treg cells, and possibly other T cell subsets, in the intestines. However, the mechanisms involved remain unclear. In this report, we investigated how SCFA regulate development and function of microbiota antigen-specific T cells. We treated CBir1 transgenic T cells, specific for an immunodominant microbiota antigen CBir1 flagellin, with SCFA under various T cell polarization conditions to determine how they regulate T cell differentiation, and transferred those T cells into RAG−/− mice to determine their function in induction of colitis. Our results demonstrated that C2, C3 and C4 all promoted T cell production of IFN-γ and IL-10 when cultured under neutral and Th1 conditions. Under Th17 conditions C2, C3 promoted, while C4 inhibited, T cell IL-17 production at early stage of cell divisions. However, all three SCFA promoted T cell IL-10 production. Mechanistically, SCFA activation of mTOR pathway but not inhibition of HDAC or binding GPR43 mediated their effects on Th1 and Th17 cells. Functionally, transfer of C2- and C4-treated Th1 and Th17 cells induced less severe colitis in RAG−/− mice compared to untreated T cells, probably through induction of IL-10 by those T cells. Collectively, our study indicated that SCFA differentially regulate T cells differentiation and function in the intestines, which could contribute the maintenance of intestinal homeostasis." @default.
- W4313360052 created "2023-01-06" @default.
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- W4313360052 date "2017-05-01" @default.
- W4313360052 modified "2023-09-23" @default.
- W4313360052 title "Short chain fatty acids differentially regulate differentiation and function of Th1 and Th17 cells in the intestines" @default.
- W4313360052 doi "https://doi.org/10.4049/jimmunol.198.supp.65.16" @default.
- W4313360052 hasPublicationYear "2017" @default.
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