Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis
Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis
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DOI：
10.1038/s41467-020-15855-z
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发表时间：
2020-04-24
影响因子：
16.6
通讯作者：
Zaiss, Mario M.
中科院分区：
文献类型：
--
作者：
Azizov, Vugar;Dietel, Katharina;Zaiss, Mario M.
饮酒是自身免疫性疾病发展的始终如一的保护因素，如类风湿关节炎(RA)。然而，酒精诱导耐受性的潜在机制尚不清楚。在此，我们展示了酒精及其代谢物醋酸酯在体外和体内改变了T滤泡辅助细胞(T-FH)的功能状态，从而发挥了免疫调节和诱导耐受的特性。酒精暴露的小鼠减少了Bcl6和PD-1的表达以及T-FH细胞产生IL-21，阻止了T-FH细胞在生发中心形成T-FH：B细胞的适当空间组织。这种作用与自身抗体的形成受损有关，并可减轻实验性自身免疫性关节炎。相比之下，非T细胞免疫反应和被动关节炎模型不会受到酒精暴露的影响。这些数据阐明了饮酒的免疫调节和耐受诱导作用。适度饮酒与预防某些自身免疫性疾病有关。研究表明，乙醇及其代谢物醋酸酯对胶原性关节炎小鼠有保护作用，其作用机制可能与抑制T滤泡辅助细胞的效应功能有关。
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. Moderate consumption of alcohol is associated with protection from some autoimmune diseases. Here the authors show that ethanol and its metabolite acetate can protect mice from collagen-induced arthritis and provide evidence that the mechanism of this effect might be via inhibition of the effector function of T follicular helper cells.