Journal Article Review Ppublish 3 citations
PubMed: 42649250 DOI: 10.1038/s41584-026-01421-2
Hepatic control of immunometabolism: implications for the pathogenesis, diagnosis and treatment of rheumatic diseases.
Nat Rev Rheumatol 22(11):675-695
Authors: Andras Perl, Katalin Banki
Affiliations
- Departments of Medicine, Microbiology and Immunology, and Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Norton College of Medicine, Syracuse, NY, USA.
- Department of Pathology, State University of New York Upstate Medical University, Norton College of Medicine, Syracuse, NY, USA.
Abstract
Autoimmune rheumatic diseases, including systemic lupus erythematosus and antiphospholipid syndrome, arise from interactions between genetic susceptibility and environmental triggers that drive metabolic dysregulation. The liver, a central metabolic and immunological organ, has a key role in initiating and amplifying systemic autoimmunity and organ damage. It functions as an interface between the gut microbiome, nutrients, drugs and environmental toxins. The liver regulates immune cell development, coordinates systemic immune responses through metabolite and cytokine production and modifies self-antigens via oxidation, glycosylation and lipidation. These changes can transform normal molecules into autoantigens. Hepatocytes also produce coagulation, complement factors and apolipoproteins, such as β 2-glycoprotein I, a major target of antiphospholipid antibodies. In addition, the liver secretes antioxidants such as glutathione, albumin and paraoxonase-1, which protect lipoproteins from becoming antigenic and reduce risks of atherosclerosis and thrombosis. Liver diseases such as steatosis and steatohepatitis have bidirectional relationships with systemic lupus erythematosus, antiphospholipid syndrome and other rheumatic conditions. Liver cells can also be direct targets of autoimmune responses. Delineating the role of the liver in metabolic control of autoimmunity and inflammation can lead to better understanding of disease pathogenesis, improved clinical diagnosis and identification of new therapeutic targets in rheumatic diseases.
MeSH
Cells, Hepatocytes, Lipoproteins, Liver, Rheumatic Diseases, Lupus Erythematosus, Systemic, Antiphospholipid Syndrome, Immunity, Diagnosis, Therapeutics, Autoantigens, Autoimmunity