Regulatory T cells in autoimmune liver diseases

Abstract

Autoimmune liver diseases (AILDs), including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and IgG4-related sclerosing cholangitis, are characterised by immune dysregulation that adversely affects the hepatocytes or bile ducts. Regulatory T cells (Tregs), which are pivotal for immune tolerance, display altered function and abundance across these disorders, with notable differences between peripheral and hepatic environments. This review synthesises current evidence on disease-specific Treg alterations across AILDs, integrating findings from human studies and preclinical models. We highlight heterogeneity in Treg abundance, phenotype and function across disease subtypes, stages and tissue compartments, while examining the influence of the local immune microenvironment and gut-liver axis on Treg stability and function. We further evaluate current and emerging Treg-targeted therapeutic strategies, ranging from restoration of Treg abundance and function to disease-specific modulation of Treg responses, together with the major challenges to their clinical translation. By integrating these findings, we provide a disease-dependent and context-dependent framework for understanding Treg dysregulation in AILDs and identify key priorities for future mechanistic and translational research.