Multiple sclerosis (MS) is an autoimmune, demyelinating, and neurodegenerative disease of the central nervous system (CNS) that affects 2-2.5 million people worldwide. Although the etiology of MS is not well known, MS is widely considered to be an autoimmune disease. Currently approved MS drugs reduce relapse rates but fail to reverse or prevent neurodegeneration and disability progression. Increasing evidence indicates that microglia and major histocompatibility complex class II (MHC II) expression in these cells play important roles in the pathophysiology of MS. For a T cell to contribute to CNS pathogenesis, it must be reactivated by antigen-presenting cells within the CNS parenchyma. Susceptibility to MS is associated with MHC II genes, suggesting that presentation of antigens on MHC II plays an important role in CD4+ T-cell reactivation and disease initiation. An ERβ-selective agonist was previously reported to suppress reactivation of T cells invading the spinal cord, thereby reducing the severity of symptoms and decreasing mortality in the first 2 weeks after disease onset. However, the mechanism by which the expression of MHC II in microglia is regulated by ERβ-selective agonists is still unclear. Therefore, we hypothesize that ERβ-selective agonists inhibit MHC II expression in microglia via inhibition of class II trans-activator (CIITA) expression by a mechanism involving inhibition of the translocation of IFNγ regulatory factor (IRF-1) to the nucleus, thereby inhibiting the inflammatory response and symptoms in the MS model.
Keywords: ERβ; Multiple sclerosis; experimental autoimmune encephalomyelitis; major histocompatibility complex class II; microglia.