TGFB1 and systemic sclerosis: In addition, fibrotic mediators in SSc-ILD, including fibronectin-EDA and tenascin-C, may trigger activation of Toll Like Receptor 4 (TLR4) (31, 32) and cause uncontrolled ECM deposition in SSc (33), which subsequently potentiates TGF-β signaling, thereby enhancing fibrotic responses (15, 34).