Estrogen Receptors in Immunity and Autoimmunity

Due to the female predominance of autoimmune diseases, the role of gender and sex hormones in the immune system is of long-term interest. Estrogen's primary effects are mediated via estrogen receptors alpha and beta (ER alpha/beta) that are expressed on most immune cells. ERs are nuclear hormone receptors that can either directly bind to estrogen response elements in gene promoters or serve as cofactors with other transcription factors (i.e., NFkB/AP1). Cytoplasmic ER and membrane associated ER impact specific kinase signaling pathways. ERs have prominent effects on immune function in both the innate and adaptive immune responses. Genetic deficiency of ER alpha in murine models of lupus resulted in significantly decreased disease and prolonged survival, while ER beta deficiency had minimal to no effect in autoimmune models. The protective effect of ER alpha in lupus is multifactoral. In arthritis models, ER alpha agonists appears to mediate a protective effect. The modulation of ER alpha function appears to be a potential target for therapy in autoimmunity.