Figure 2.

Hypothetic mechanism of FasL/IL6 selection of prefibrotic fibroblast in scleroderma lesions. After vascular damage, various factors are directly secreted by apoptotic endothelial cells or are secreted by macrophages, T cells, and fibroblasts in response to endothelial cell deaths and subsequent hypoxia. More proximal cells become prefibrotic by increasing their response to TGFβ. IL-6 secretion induces a more fibrotic phenotype for cells and increases apoptosis-resistant feature of profibrotic ones. FasL secreted by infiltrating cells kills nonfibrotic fibroblast with low or none effect on fibrotic cells. ECM is then deposited in excess and organ fails.