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Alcohol-sourced acetate reduces T cell filamentous actin branching and migration

View ORCID ProfileVugar Azizov, View ORCID ProfileMichael Frech, Jörg Hofmann, Marketa Kubankova, View ORCID ProfileDennis Lapuente, View ORCID ProfileMatthias Tenbusch, View ORCID ProfileJochen Guck, View ORCID ProfileGeorg Schett, View ORCID ProfileMario M. Zaiss
doi: https://doi.org/10.1101/2022.03.08.483253
Vugar Azizov
1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
2Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
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Michael Frech
1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
2Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
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Jörg Hofmann
3Division of Biochemistry, Department of Biology, Friedrich-Alexander-University Erlangen-Nürnberg; Erlangen, Germany
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Marketa Kubankova
4Max Planck Institute for the Science of Light & Max Planck Zentrum für Physik und Medizin; Erlangen, Germany
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Dennis Lapuente
5Institute of Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
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Matthias Tenbusch
5Institute of Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
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Jochen Guck
4Max Planck Institute for the Science of Light & Max Planck Zentrum für Physik und Medizin; Erlangen, Germany
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Georg Schett
1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
2Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
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Mario M. Zaiss
1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
2Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
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  • For correspondence: mario.zaiss@uk-erlangen.de
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Abstract

Alcohol is among the most widely consumed dietary substances. While excessive alcohol consumption damages the liver, heart and brain, clinical observations suggest that alcohol has strong immunoregulatory properties. Mechanisms by which alcohol undermines immune cell functions during autoimmunity and vaccination are currently elusive. Herein, we show that acetate, the main metabolite of alcohol, effectively inhibits the migratory capacity of T cells through acetylation of cortactin, a protein which stabilizes and promotes branching of filamentous actin. Acetate-induced cytoskeletal changes effectively inhibited activation, proliferation, and immune synapse formation in T cells at tissue concentrations reached by alcohol consumption. In summary, these data show that acetate inhibits T cell-mediated immune responses by modulating the T cell cytoskeletal biomechanics.

One-Sentence Summary Exposure to elevated acetate concentrations change T cell biomechanics, reducing cell migration and immune synapse formation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 09, 2022.
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Alcohol-sourced acetate reduces T cell filamentous actin branching and migration
Vugar Azizov, Michael Frech, Jörg Hofmann, Marketa Kubankova, Dennis Lapuente, Matthias Tenbusch, Jochen Guck, Georg Schett, Mario M. Zaiss
bioRxiv 2022.03.08.483253; doi: https://doi.org/10.1101/2022.03.08.483253
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Alcohol-sourced acetate reduces T cell filamentous actin branching and migration
Vugar Azizov, Michael Frech, Jörg Hofmann, Marketa Kubankova, Dennis Lapuente, Matthias Tenbusch, Jochen Guck, Georg Schett, Mario M. Zaiss
bioRxiv 2022.03.08.483253; doi: https://doi.org/10.1101/2022.03.08.483253

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