GPBAR1-mediated bile acid sensing in cholangiocytes drives IL-23/Th17-dependent inflammation in PSC

Primary sclerosing cholangitis (PSC) is a progressive cholangiopathy characterized by bile duct inflammation, fibrosis, and increased risk of cholangiocarcinoma. Here we identify the IL-23/IL-17 axis as a central amplifier of PSC and demonstrate that PBT002, an hybrid dual GPBAR1/RORγt ligand, restores immune and metabolic balance in preclinical models.