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

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.