Is T-bet a Potential Therapeutic Target in Multiple Sclerosis?

Abstract

Treatments for multiple sclerosis (MS) have changed over the past years as our understanding of immunology and neuroscience has evolved. Experimental autoimmune encephalomyelitis (EAE) continues to remain the major model for MS and has been a major vehicle in the development of new therapeutic targets for MS, including new agents such as natalizumab, fingolimod, and dimethyl fumarate. As progress in the molecular understanding of immunology continues, many observations in EAE are pursued with the ultimate goal of defining the pathophysiology of MS and development of innovative treatments for the disease. Although many consider MS to be a T cell-mediated autoimmune disease directed against myelin antigens, the exact cause of the disease is still unknown. For many years, it was thought that myelin-specific T cells that secreted interferon-γ and were proinflammatory were the major T cell subset that mediated the disease, but recent studies on the cytokine phenotype of pathogenic T cells in EAE and MS have opened debate on this issue. Work over the past several years suggests that the transcription factor T-bet appears to be an important factor in T cell encephalitogenicity; however, recent data suggest that it is also dispensable in certain situations, particularly for Th17 cells. Understanding the molecular mechanisms responsible for T cell encephalitogenicity in MS and other autoimmune diseases will be essential in the development of specific therapies for these inflammatory diseases.