Figure 3.

The role of platelets in SSc pathophysiology. Ischemia-reperfusion injury associated endothelial cell damage induces platelet activation. Similar to SLE, the presence of ICs could promote hypersensitivity of platelets and complement activation. Activated platelets release their profibrotic mediators such as TGF-β, serotonin and PDGF, and these factors stimulate connective tissue fibroblasts proliferation and increase collagen production. In addition, both HMGB1 released from platelets and complement activation can support NET formation and ROS release, which further mediates vascular endothelial dysfunction. Apart from NETs, platelets derived PF4 activates endothelial cells and induces SSc associated vascular damage. Activated platelets also release sCD40L to active B cells through CD40 signaling, which leads to B cell auto-antibody production. Moreover, sCD40L and serotonin can promote the maturation of myeloid DCs, followed by IFN production and further B cell activation.