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

• Published in: Science signaling 2018-04, Vol.11 (526)
• Main Authors: Mohammad, Imran, Starskaia, Inna, Nagy, Tamas, Guo, Jitao, Yatkin, Emrah, Väänänen, Kalervo, Watford, Wendy T, Chen, Zhi
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Cell activation; Cell proliferation; Clonal deletion; Colitis; Cytokines; Disorders; Estrogens; Etiology; Females; Foxp3 protein; Hormones; Immunoregulation; Immunotherapy; Inflammation; Inflammatory bowel disease; Lymphocytes; Lymphocytes T; Phenotypes; Risk factors; Sex hormones; Sex linkage
• ISSN: 1945-0877; 1937-9145
• DOI: 10.1126/scisignal.aap9415

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 , 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.