Endogenous ligands for TLRs in SSc include ECM molecules (e.g., alternatively-spliced fibronectins, abbreviated as Fn-EDA, induced by TGF-β in normal fibroblasts), cellular stress proteins (high-mobility group protein B1, abbreviated as HMGB1, and HSP60), and nucleic-acid-containing immune complexes [4,7,55]. This evidence concerns the gene HMGB1 and systemic sclerosis.