Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation

Azizov V, Hübner M, Frech M, Hofmann J, Kubankova M, Lapuente D, Tenbusch M, Guck J, Schett G, Zaiss M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

iScience Elsevier

Book Volume: 26

Article Number: 107230

Journal Issue: 7

DOI: 10.1016/j.isci.2023.107230

Abstract

Alcohol is among the most widely consumed dietary substances. Excessive alcohol consumption damages the liver, heart, and brain. Alcohol also has strong immunoregulatory properties. Here, we report how alcohol impairs T cell function via acetylation of cortactin, a protein that binds filamentous actin and facilitates branching. Upon alcohol consumption, acetate, the metabolite of alcohol, accumulates in lymphoid organs. T cells exposed to acetate, exhibit increased acetylation of cortactin. Acetylation of cortactin inhibits filamentous actin binding and hence reduces T cell migration, immune synapse formation and activation. While mutated, acetylation-resistant cortactin rescues the acetate-induced inhibition of T cell migration, primary mouse cortactin knockout T cells exhibited impaired migration. Acetate-induced cytoskeletal changes effectively inhibited activation, proliferation, and immune synapse formation in T cells in vitro and in vivo in an influenza infection model in mice. Together these findings reveal cortactin as a possible target for mitigation of T cell driven autoimmune diseases.

Authors with CRIS profile

Vugar Azizov Department of Medicine 3 – Rheumatology and Immunology Michael Frech Department of Medicine 3 – Rheumatology and Immunology Jörg Hofmann Lehrstuhl für Biochemie Dennis Lapuente Institute of Clinical and Molecular Virology Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren Jochen Guck
Georg Schett Lehrstuhl für Innere Medizin III Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE)

How to cite

APA:

Azizov, V., Hübner, M., Frech, M., Hofmann, J., Kubankova, M., Lapuente, D.,... Zaiss, M. (2023). Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation. iScience, 26(7). https://doi.org/10.1016/j.isci.2023.107230

MLA:

Azizov, Vugar, et al. "Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation." iScience 26.7 (2023).

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