What are the new milestones in the pathogenesis of systemic sclerosis?

Abstract

Systemic sclerosis (SSc) is a chronic inflammatory autoimmune disease involving the connective tissue of the skin and various internal organs. In recent years research on SSc has evolved to provide a better understanding of the interdependence of the three major systems involved—namely, the vascular system, the immune system and the connective tissue. Hypoxia is increasingly recognised as a decisive factor in modulating the inflammatory process in SSc, activating fibroblasts and changing their phenotype. In addition, several mediators synthesised by immune cells, including cytokines such as transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF), cooperate in inducing the activation of fibroblasts and their differentiation into myofibroblasts. Therefore, a variety of intracellular and extracellular strategies to inhibit the activity of TGFβ and PDGF are currently receiving intense investigation. To further improve our therapeutic strategies for this paradigmatic fibrotic disease, an improved understanding of connective tissue remodelling as it takes place in the different stages of SSc will be imperative.