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- W2911672024 abstract "Abstract Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is a potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Mechanistically, this reprogramming is mediated by supplying additional pentanoate-originated acetyl-CoA for histone acetyltransferases, and by pentanoate-triggered enhancement of mTOR activity. In experimental mouse models of colitis and multiple sclerosis, pentanoate-induced regulatory B cells mediate protection from autoimmune pathology. Additionally, pentanoate shows a potent histone deacetylase-inhibitory activity in CD4 + T cells, thereby reducing their IL-17A production. In germ-free mice mono-colonized with segmented filamentous bacteria (SFB), pentanoate inhibits the generation of small-intestinal Th17 cells and ameliorates SFB-promoted inflammation in the central nervous system. Taken together, by enhancing IL-10 production and suppressing Th17 cells, the SCFA pentanoate might be of therapeutic relevance for inflammatory and autoimmune diseases." @default.
- W2911672024 created "2019-02-21" @default.
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- W2911672024 date "2019-02-15" @default.
- W2911672024 modified "2023-10-15" @default.
- W2911672024 title "The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes" @default.
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- W2911672024 doi "https://doi.org/10.1038/s41467-019-08711-2" @default.
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