Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis
Vugar Azizov, Katharina Dietel, Franziska Steffen, Kerstin Dürholz, Julia Meidenbauer, Sébastien Lucas, Michael Frech, Yasunori Omata, Narges Tajik, Lisa Knipfer, Anne Kolenbrander, Silvia Seubert, Dennis Lapuente, Maria Sokolova, Jörg Hofmann, Matthias Tenbusch, Andreas Ramming, Ulrike Steffen, Falk Nimmerjahn, Ralf A. Linker, Stefan Wirtz, Martin Herrmann, Vladimir Temchura, Kerstin Sarter, Georg Schett, Mario M. Zaiss
Abstract
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 (T FH ) 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 T FH cells, preventing proper spatial organization of T FH cells to form T FH :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.