Scleroderma: recent lessons from murine models and implications for future therapeutics

Abstract

Systemic sclerosis (SSc) is an autoimmune disease marked by excessive extracellular matrix deposition in the skin and internal organs. Although the etiology of SSc remains unknown, three major abnormalities are considered to play important roles in the pathophysiology of SSc: autoimmunity, vasculopathy and fibrosis. Mouse models are critical tools for further understanding of the pathophysiology underlying this disease. The bleomycin-induced scleroderma model and TSK/+ mice are the primary SSc models; however, emerging models of SSc, such as Fra-2 Tg mice and the hypochlorous acid (HOCl)-induced scleroderma model, have provided novel insights into the pathophysiology of SSc. Importantly, a growing number of studies suggests a role for B cells, including regulatory B cells, in the pathogenesis of SSc. Thus, for the development of therapies, targeting of profibrogenic cytokines, such as transforming growth factor-β is still a very active area of investigation and B cell-targeted therapies also represent pot...