595 Type I interferon contributes to vasculopathy and accelerated fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is one of the most devastating autoimmune diseases characterized by vasculopathy and fibrosis that affects both skin internal organs. IFN signature present in blood SSc patients. Polymorphisms regulatory genes IRF-4,5,7,8 STAT4 have been found to be associated with SSc. Despite these evidence, exact role remains poorly understood. We performed single-cell RNA sequencing on from patients diffuse SSc(dSSc), limited SSc(lSSc) normal controls. Higher type I interferon response was endothelium dSSc compared lSSc Gene expression endothelial-to-mesenchymal transition (EndoMT) also elevated These findings were confirmed another dataset. verified our protein level cohort higher disease progression. Interestingly, bleomycin-induced mouse model, administration IFNα AAV (adeno-associated virus) significantly accelerated EndoMT. In conclusion, data suggests a pathological fibrosis, which support blockade treatment.