Sex hormones and epigenetic dysregulation in autoimmune disease

Healthy individuals exhibit sex-specific immune responses. In certain immune-related diseases, such as autoimmune diseases, there is a pronounced sex bias in incidence, severity, and other clinical features. These differences are influenced by immune-related genes encoded in the sex chromosomes, as well as by genes whose expression is regulated by sex hormones. Sex hormone receptors play key roles in gene expression regulation by inducing epigenetic modifications and chromatin structure changes, thereby influencing the properties of immune cells at multiple levels. In this review, we provide an overview of the pathways activated by sex hormones and their receptors, highlighting their interplay with the epigenetic machinery that shapes the properties of immune cells in both females and males. We then examine the implications of sex hormone-associated epigenetic dysregulation in autoimmune diseases. Finally, we discuss current and potential clinical implications to enhance understanding of pathophysiology and the prospects for biomarkers and therapy. This review offers valuable insights into the roles of sex hormones and the mechanisms governing immune function and pathogenesis.