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

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Details zur Publikation

Autorinnen und Autoren: 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
Zeitschrift: Nature Communications
Jahr der Veröffentlichung: 2019
Band: 10
ISSN: 2041-1723


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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Hofmann, Jörg Dr.
Lehrstuhl für Biochemie
Zaiss, Mario PD Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie


Einrichtungen weiterer Autorinnen und Autoren

Hebrew University of Jerusalem
Philipps-Universität Marburg


Zitierweisen

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).

BibTeX: 

Zuletzt aktualisiert 2019-27-02 um 16:38