Systemic Sclerosis and the Immune System: From Pathways to Targets

Systemic sclerosis is a rare connective tissue disorder characterized by a widespread thrombotic microangiopathy, excessive deposition of extracellular matrix components in the skin and internal organs causing systemic fibrosis, associated to immune dysfunction affecting both innate and adaptive immunity. The immune dysregulation appears earlier in the course of the disease, and the innate immunity components seem to react to vascular antigens released following endothelial cells apoptosis, thus initiating the adaptive immunity. Via a cytokines network, the immune system provides a profibrotic environment in which fibroblasts thrive with excess secretion of extracellular matrix components. Once activated, the adaptive immunity acts as an amplifier of these disorders whether by sustaining the pro-fibrotic environment (by T helper 2 cells), promoting auto-antibodies secretion (by B Cells), or via disruption of suppressive cells (regulatory T cells). The intricacy of these immunological aspects offers an explanation as to why classical immunosuppressors fall short when it comes to managing systemic sclerosis, asserting the need for newer and more specific molecules.