The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes

Luu M, Pautz S, Kohl V, Singh R, Romero R, Lucas S, Hofmann J, Raifer H, Vachharajani N, Carrascosa LC, Lamp B, Nist A, Stiewe T, Shaul Y, Adhikary T, Zaiss M, Lauth M, Steinhoff U, Visekruna A (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 10

Article Number: 760

DOI: 10.1038/s41467-019-08711-2

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 monocolonized 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.

Authors with CRIS profile

Jörg Hofmann Lehrstuhl für Biochemie Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Philipps-Universität Marburg DE Germany (DE) Hebrew University of Jerusalem IL Israel (IL)

How to cite

APA:

Luu, M., Pautz, S., Kohl, V., Singh, R., Romero, R., Lucas, S.,... Visekruna, A. (2019). The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes. Nature Communications, 10. https://dx.doi.org/10.1038/s41467-019-08711-2

MLA:

Luu, Maik, et al. "The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes." Nature Communications 10 (2019).

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