Molecular Mechanisms Behind the Role of Plasmacytoid Dendritic Cells in Systemic Sclerosis

SIMPLE SUMMARY: Systemic Sclerosis (SSc) is a rare autoimmune disease characterized by scarring of the tissues and organs. This scarring, or fibrosis, has a major impact on a patient’s quality of life; for example, lung fibrosis reduces the efficiency of breathing and is a significant cause of death for SSc patients. To develop novel therapeutic strategies, it is important to understand what causes fibrosis to occur and progress. It was recently found that plasmacytoid dendritic cells (pDCs) are key immune cells in the development of fibrosis in SSc. These cells are innate immune cells that are specialized in anti-viral responses, and they are also involved in autoimmune diseases. This review will examine the recent research that has started to uncover the molecular mechanisms through which pDCs impact SSc. ABSTRACT: Systemic sclerosis (SSc) is a debilitating autoimmune disease that affects multiple systems. It is characterized by immunological deregulation, functional and structural abnormalities of small blood vessels, and fibrosis of the skin, and, in some cases, internal organs. Fibrosis has a devastating impact on a patient’s life and lung fibrosis is associated with high morbimortality. Several immune populations contribute to the progression of SSc, and plasmacytoid dendritic cells (pDCs) have been identified as crucial mediators of fibrosis. Research on murine models of lung and skin fibrosis has shown that pDCs are essential in the development of fibrosis, and that removing pDCs improves fibrosis. pDCs are a subset of dendritic cells (DCs) that are specialized in anti-viral responses and are also involved in autoimmune diseases, such as SSc, systemic lupus erythematosus (SLE) and psoriasis, mostly due to their capacity to produce type I interferon (IFN). A type I IFN signature and high levels of CXCL4, both derived from pDCs, have been associated with poor prognosis in patients with SSc and are correlated with fibrosis. This review will examine the recent research on the molecular mechanisms through which pDCs impact SSc.