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

Author

Listed:
  • Maik Luu

    (Philipps-University Marburg)

  • Sabine Pautz

    (Philipps-University Marburg
    University of Kassel)

  • Vanessa Kohl

    (Philipps-University Marburg)

  • Rajeev Singh

    (Philipps-University Marburg)

  • Rossana Romero

    (Philipps-University Marburg)

  • Sébastien Lucas

    (Friedrich-Alexander-University-Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Jörg Hofmann

    (Friedrich-Alexander-University-Erlangen-Nürnberg)

  • Hartmann Raifer

    (Philipps-University Marburg)

  • Niyati Vachharajani

    (Philipps-University Marburg
    Vanderbilt University Medical Center)

  • Lucia Campos Carrascosa

    (Philipps-University Marburg)

  • Boris Lamp

    (Philipps-University Marburg)

  • Andrea Nist

    (Philipps-University Marburg)

  • Thorsten Stiewe

    (Philipps-University Marburg
    Philipps-University Marburg)

  • Yoav Shaul

    (The Hebrew University-Hadassah Medical School)

  • Till Adhikary

    (Philipps-University Marburg)

  • Mario M. Zaiss

    (Friedrich-Alexander-University-Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Matthias Lauth

    (Philipps-University Marburg)

  • Ulrich Steinhoff

    (Philipps-University Marburg)

  • Alexander Visekruna

    (Philipps-University Marburg)

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.

Suggested Citation

  • Maik Luu & Sabine Pautz & Vanessa Kohl & Rajeev Singh & Rossana Romero & Sébastien Lucas & Jörg Hofmann & Hartmann Raifer & Niyati Vachharajani & Lucia Campos Carrascosa & Boris Lamp & Andrea Nist & T, 2019. "The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08711-2
    DOI: 10.1038/s41467-019-08711-2
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    Cited by:

    1. Lizhen Zhu & Geng Li & Zhixin Liang & Tuan Qi & Kui Deng & Jiancheng Yu & Yue Peng & Jusheng Zheng & Yan Song & Xing Chang, 2023. "Microbiota-assisted iron uptake promotes immune tolerance in the intestine," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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