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Journal Article
Review
Systemic sclerosis: Is the epithelium a missing piece of the pathogenic puzzle?
Journal of Dermatological Science 2019 May
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by three cardinal pathological features, such as autoimmunity/inflammation, vasculopathy and extensive organ fibrosis. Therefore, numerous interests have been put on the roles of immune cells, vascular cells (endothelial cells and pericytes/vascular smooth muscle cells) and interstitial fibroblasts as well as their precursors in the field of SSc research. However, recent studies with clinical samples and animal models have drawn much attention to the potential role of epithelial cells as a member of critical drivers and/or modifiers in the pathogenesis of SSc. Indeed, phenotypically altered epithelial cells possibly explain the selective organ fibrosis in the skin, esophagus and lung, the origin of autoimmunity and Köbner phenomenon-associated localized scleroderma-like lesions, the mechanisms of which had remained unknown in the canonical idea of SSc pathogenesis. This article overviews the recent progress in understanding the contribution of epithelial cells to the pathogenesis of SSc. Although further studies are required to confirm the potential role of epithelial cells in SSc development, this notion may provide us with a missing piece of the puzzle to solve the unanswered questions in the pathogenesis of SSc.
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