Plasmacytoid dendritic cells correlate with fibrosis in patients with systemic sclerosis and contribute to fibrosis in a murine model (P3133)

Abstract

Abstract Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis in multiple organs including skin and lung. Mechanisms that drive fibrosis in SSc remain unclear. Here, we report the role of dendritic cells (DC) in SSc, with a focus on plasmacytoid DC (pDC) subset. We found that whereas pDC were reduced in the blood of patients with SSc as compared to healthy controls, these cells accumulated in target organs such as skin and lungs. In the lung lavage fluid (BAL), pDC frequency correlated with CT scores of SSc-interstitial lung disease (ILD) and with a set of proteins involved in inflammation, leukocyte migration, and wound repair. Importantly, pDC were reduced in the BAL of SSc patients after treatment with imatinib mesylate that has been previously reported to improve, albeit modestly, skin score and lung function. To directly investigate the role of pDC in vivo, we depleted pDC in mice injected with bleomycin that induces SSc-like disease. pDC-depleted mice had reduced skin and lung disease compared to controls. Thus, we provide several lines of evidence in humans and mice supporting a role of pDC in SSc pathogenesis. Ongoing studies will investigate mechanisms that lead to increased migration of pDC from blood to target organs and/or their local expansion in humans and mice with SSc.