Estrogen and Signaling in the Cells of Immune System

Hypothalamus-pituitary-gonadal axis regulation of estrogen, which acts on reproductive tissues, is well established. However, it is also evident that estrogens physiologically act on not only reproductive tissues but also on a broad range of tissues such as immune system. It is well documented that estrogen regulates all facets of the immunoregulation thereby affecting the outcome of autoimmune and inflammatory immune responses. Given the broader role of estrogen in immunobiology, it is important to understand how estrogens act on the cells of the immune system. Estrogens act in estrogen receptor dependent and/or independent manner to affect the regulation of cytokines and chemokines. This review focuses on sources and biosynthesis of estrogens, differential expression of estrogen receptors on the cells of immune system, key signaling pathways and its effect on the induction of key pro- and anti-inflammatory cytokines. Since estrogen has contrasting effects in female-predominant autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE), we briefly overview the mechanistic role of estrogen on these chronic diseases. Recent evidence suggests that estrogens also alter microRNAs, which regulate a broad range of transcription of genes. The review also addresses this and other newly discovered mechanisms of estrogen-induced immunomodulation in health and disease.