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.
Highlights
Alcohol consumption is a consistent protective factor for the development of autoimmune diseases such as rheumatoid arthritis (RA)
To investigate the effects of alcohol on arthritis, we induced mice for collageninduced arthritis (CIA) by immunizing DBA/1 mice with CII in complete Freund adjuvant (CFA) on days 0 and 21 and simultaneously started treatment with either 10% ethanol in drinking water (CIA + EtOH) or water alone starting on day 0 (Fig. 1a)
To further assess the role of ethanol in the initiation stage of CIA, we explored total IgG serum levels in mice induced for CIA
Summary
Alcohol consumption is a consistent protective factor for the development of autoimmune diseases such as rheumatoid arthritis (RA). Alcohol-exposed mice have reduced Bcl[6] 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. T cell independent immune responses and passive models of arthritis are not affected by alcohol exposure. These data clarify the immune regulatory and toleranceinducing effect of alcohol consumption. Moderate alcohol consumption has consistently been identified as protective factor for the onset of rheumatoid arthritis (RA)[5,6] and systemic lupus erythematosus (SLE)[7]
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