TLR4 endogenous ligands [including fibronectin, hyaluronan fragments, heat-shock protein (HSP) 70, HSP9, high-mobility group box-1 (HMGB-1), and S100A proteins] could engage TLR4 (which is increased in SSc skin and lungs) and synergize with TGF-β to increase fibroblast CI production (155–160). This evidence concerns the gene HMGB1 and systemic sclerosis.