Molecular mechanisms underlying T cell subset imbalance and precision therapeutic targets in primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive destruction of small intrahepatic bile ducts and cholestasis-associated hepatic fibrosis. Although ursodeoxycholic acid and second-line agents improve biochemical indices in many patients, approximately 10%-20% still progress to cirrhosis or require liver transplantation. This therapeutic gap reflects the bidirectional, self-amplifying interplay between intrahepatic cholestasis and immune dysregulation, while the core immunopathological mechanisms remain incompletely defined and single-effector cell-centered models are insufficient to explain bile duct-targeted injury. Within this context, T cell subset imbalance has emerged as a key conceptual framework for precision intervention. This review synthesizes current evidence on T cell subset imbalance in PBC and posits that T cell heterogeneity and network dysregulation constitute both a central pathogenic basis and a rational therapeutic target. Specifically, imbalance of the Th17/Treg ratio among CD4