Estrogen receptor α contributes to T cell-mediated autoimmune inflammation by promoting T cell activation and proliferation

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. (ER alpha) contributes to autoimmune diseases, we generated mice in which ER alpha was deleted specifically in T lymphocytes. We found that ER alpha deletion in T cells reduced their pathogenic potential in a mouse model of colitis and correlated with transcriptomic changes that affected T cell activation. ER alpha 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 ER alpha in T cells plays an important role in inflammation and suggest that ER alpha-targeted immunotherapies could be used to treat autoimmune disorders.