Primary Sclerosing Cholangitis (PSC)

PSC is a chronic disease of the biliary tree, characterized by obliterative fibrosis of the intrahepatic and/or extrahepatic bile ducts and chronic portal tract inflammation, eventually leading to cirrhosis and portal hypertension and cholangiocarcinoma. The etiology and pathogenesis of PSC remain unknown. The pathogenesis of PSC is still unknown and the lack of a satisfactory animal or cellular model orthologous to human PSC has hampered the search for a cure. Based on our studies on CFLD showing that dysregulated innate immune signaling causes the biliary epithelium to have an exaggerated inflammatory response to changes in microbiota and intestinal permeability, our working hypothesis is that an increased inflammatory response of the biliary epithelium to stimulation of the innate immunity pathways plays an important role in the pathogenesis of PSC. We are addressing this hypothesis using human cellular models, such as iPSC-derived cholangiocytes and biliary spheroids (organoids), as also discussed below.