It has long been appreciated that most autoimmune disorders are characterized by increased prevalence in females, suggesting a potential role for sex hormones in the etiology of autoimmunity. To study how estrogen receptor α (ERα) contributes to autoimmune diseases, we generated mice in which ERα was deleted specifically in T lymphocytes. We found that ERα deletion in T cells reduced their pathogenic potential in a mouse model of colitis and correlated with transcriptomic changes that affected T cell activation. ERα deletion in T cells contributed to multiple aspects of T cell function, including reducing T cell activation and proliferation and increasing the expression of Foxp3, which encodes a critical transcription factor for the differentiation and function of regulatory T cells. Thus, these data demonstrate that ERα in T cells plays an important role in inflammation and suggest that ERα-targeted immunotherapies could be used to treat autoimmune disorders.

长期以来人们一直认识到，大多数自身免疫性疾病的特征是女性患病率升高，这表明性激素在自身免疫性病因中具有潜在作用。为了研究雌激素受体α（ERα）如何导致自身免疫疾病，我们生成了其中ERα在T淋巴细胞中特异性缺失的小鼠。我们发现，T细胞中的ERα缺失降低了结肠炎小鼠模型的致病潜能，并与影响T细胞活化的转录组学变化相关。T细胞中的ERα缺失有助于T细胞功能的多个方面，包括减少T细胞的活化和增殖以及增加Foxp3的表达，它编码调节性T细胞的分化和功能的关键转录因子。因此，这些数据证明T细胞中的ERα在炎症中起重要作用，并提示靶向ERα的免疫疗法可用于治疗自身免疫性疾病。