Complex interplay between the immune system, metabolism, and epigenetic factors in autoimmune liver diseases

Autoimmune liver diseases (ALDs) are chronic inflammatory hepatobiliary diseases in which the autoimmune responses directed against liver tissue result in inflammation and tissue damage. There are several types of ALDs, including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, immunoglobulin G4-related sclerosing cholangitis, and overlap syndromes. Metabolism and epigenetics are both critical components of the development and progression of ALDs. Immunometabolism addresses how metabolic processes influence immune cell development, fate and behavior, and how immune responses impact metabolism. In the context of immunity, epigenetics involves regulating gene expression without altering the DNA sequence. Epigenetic modifications can ultimately result in changes in the immunophenotype. The interplay between the immune system, metabolism, and epigenetic factors is highly complex. A better understanding of this interplay and the regulatory mechanisms involved is crucial to uncover the disease pathogenesis of ALDs and exploring novel therapeutic options. This article provides a comprehensive review of the dysregulation of immunometabolism and epigenetics, as well as the multilevel regulatory mechanisms, underlying the autoimmunity in ALDs.