Decreased T cell ERK pathway signaling may contribute to the development of lupus through effects on DNA methylation and gene expression.
T cells from patients with active lupus have multiple biochemical abnormalities. One of these is DNA hypomethylation, which in model systems alters gene expression and induces lupus-like autoimmunity. Recent reports indicate that DNA methylation is regulated in part by the ERK pathway, and that ERK pathway signaling is diminished in lupus T cells. This suggests a model in which defective T cell ERK pathway signaling contributes to the development of autoimmunity by decreasing DNA methyltransferase expression, modifying DNA methylation patterns and altering gene expression. This mechanism could contribute to idiopathic and drug-induced lupus.
Oelke
Kurt
K
Department of Medicine, University of Michigan, and the Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan.
Richardson
Bruce
B
D015551:Autoimmunity; D019175:DNA Methylation; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D008177:Lupus Vulgaris / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism
D006830:Hydralazine; D008780:Methyltransferases; D020928:Mitogen-Activated Protein Kinases