Immune cell dysregulation as a mediator of fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is a destructive connective tissue disease characterized by dysregulation of the immune system and fibrosis in the skin and internal organs. The pathogenesis of SSc is complex and remains to be determined. So far, limited specific disease-modifying treatments are available for the effective control of fibrosis in patients with SSc. Studies from the past few years hint at the importance of immune dysfunctions, including the dysregulation of innate and adaptive immune cells, as well as the aberrant secretion of inflammatory and fibrotic cytokines, in the pathogenesis of SSc fibrosis. In this Review, we summarize the most pertinent findings concerning the involvement of dysregulated immune responses in fibrosis of the skin and lungs in SSc and highlight the current and potential immune-based targets for SSc therapeutics. Various types of immune cells are dysregulated in systemic sclerosis and contribute to the initiation and progression of fibrosis. In this Review, the authors summarize various immune cell defects implicated in this disease that are current or potential targets for therapy.