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Abstract：
Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.
摘要：
卵泡辅助性T（TFH）细胞介导生发中心反应，以产生针对特定病原体的高亲和力抗体，而它们的过量产生与系统性自身免疫性疾病如系统性红斑狼疮(SLE)的病发机制有关。ETV5是ETS转录因子家族的一员,在小鼠中促进TFH细胞分化。在这项研究中,我们研究了ETV5在小鼠和人类狼疮发病机制中的作用.Etv5等位基因的T细胞特异性缺失改善了狼疮小鼠模型中的TFH细胞分化和自身免疫表型。Further,我们确定SPP1为ETV5靶标,可促进小鼠和人类TFH细胞分化.值得注意的是,SPP1编码的细胞外骨桥蛋白（OPN）通过激活CD44-AKT信号通路增强TFH细胞分化。此外，SLE患者CD4+T细胞中ETV5和SPP1水平升高，与疾病活动度呈正相关。一起来看,我们的发现表明ETV5是一种促进狼疮的转录因子，分泌的OPN促进TFH细胞分化。
