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Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis

Author

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  • Vugar Azizov

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Katharina Dietel

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Franziska Steffen

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Kerstin Dürholz

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Julia Meidenbauer

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Sébastien Lucas

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Michael Frech

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Yasunori Omata

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Narges Tajik

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Lisa Knipfer

    (Department of Internal Medicine 1)

  • Anne Kolenbrander

    (Ruhr-University)

  • Silvia Seubert

    (Department of Neurology
    University Hospital Regensburg)

  • Dennis Lapuente

    (University Hospital Erlangen)

  • Maria V. Sokolova

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Jörg Hofmann

    (Department of Biology)

  • Matthias Tenbusch

    (University Hospital Erlangen)

  • Andreas Ramming

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Ulrike Steffen

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Falk Nimmerjahn

    (Institute of Genetics)

  • Ralf Linker

    (University Hospital Regensburg)

  • Stefan Wirtz

    (Department of Internal Medicine 1)

  • Martin Herrmann

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Vladimir Temchura

    (University Hospital Erlangen)

  • Kerstin Sarter

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Georg Schett

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

  • Mario M. Zaiss

    (Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
    Deutsches Zentrum für Immuntherapie (DZI))

Abstract

Alcohol consumption is a consistent protective factor for the development of autoimmune diseases such as rheumatoid arthritis (RA). The underlying mechanism for this tolerance-inducing effect of alcohol, however, is unknown. Here we show that alcohol and its metabolite acetate alter the functional state of T follicular helper (TFH) cells in vitro and in vivo, thereby exerting immune regulatory and tolerance-inducing properties. Alcohol-exposed mice have reduced Bcl6 and PD-1 expression as well as IL-21 production by TFH cells, preventing proper spatial organization of TFH cells to form TFH:B cell conjugates in germinal centers. This effect is associated with impaired autoantibody formation, and mitigates experimental autoimmune arthritis. By contrast, T cell independent immune responses and passive models of arthritis are not affected by alcohol exposure. These data clarify the immune regulatory and tolerance-inducing effect of alcohol consumption.

Suggested Citation

  • Vugar Azizov & Katharina Dietel & Franziska Steffen & Kerstin Dürholz & Julia Meidenbauer & Sébastien Lucas & Michael Frech & Yasunori Omata & Narges Tajik & Lisa Knipfer & Anne Kolenbrander & Silvia , 2020. "Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15855-z
    DOI: 10.1038/s41467-020-15855-z
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