DNA methylation and autoimmune disease.
DNA methylation plays an essential role in maintaining T-cell function. A growing body of literature indicates that failure to maintain DNA methylation levels and patterns in mature T cells can result in T-cell autoreactivity in vitro and autoimmunity in vivo. Defective maintenance of DNA methylation may be caused by drugs such as procainamide or hydralazine, or failure to activate the genes encoding maintenance DNA methyltransferases during mitosis, resulting in the development of a lupus-like disease or perhaps other autoimmune disorders. This paper reviews the evidence supporting a role for abnormal T-cell DNA methylation in causing autoimmunity in an animal model of drug-induced lupus, and discusses some of the mechanisms involved. T cells from patients with active lupus have evidence for most if not all of the same methylation abnormalities, suggesting that abnormal DNA methylation plays a role in idiopathic human lupus as well.
Richardson
Bruce
B
Department of Medicine at the University of Michigan and the Ann Arbor VA Hospital, Ann Arbor, MI 48109-0940, USA. Brichard@umich.edu
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity / Q000187:drug effects; D001374:Azacitidine / Q000633:toxicity; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D019175:DNA Methylation / Q000187:drug effects; D006801:Humans; D006830:Hydralazine / Q000633:toxicity; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000209:etiology; D018448:Models, Immunological; D011342:Procainamide / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D006830:Hydralazine; D011342:Procainamide; D001374:Azacitidine