Journal
TRANSLATIONAL RESEARCH
Volume 153, Issue 1, Pages 4-10Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.trsl.2008.10.007
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Funding
- National Center for Research Resources [P20-RR015577]
- National Institute of Allergy and Infectious Diseases [R03AI076729]
- Arthritis National Research Foundation
- University of Oklahoma College of Medicine
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR015577] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R03AI076729] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [P30AR053483] Funding Source: NIH RePORTER
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The pathogenesis of systemic lupus erythematosus (SLE) is incompletely understood. Studies in both lupus animal models and human disease indicate a clear role for epigenetic defects, particularly DNA methylation, in the pathogenesis of lupus. T-cell DNA from active lupus patients is hypomethylated, which results in overexpression of methylation-regulated genes, T-cell autoreactivity, and autoimmunity in vivo. Inducing an extracellular signal-regulated kinase (ERK) signaling defect in T cells using a transgenic mouse model resulted in reduced DNA methyltransferase 1 (DNMT1) expression, overexpression of methylation-sensitive genes, and anti-double-stranded DNA (anti-dsDNA) antibody production. ERK signaling is known to be defective in lupus T cells, and this defect is now explained by impaired T-cell protein kinase C (PKC) delta activation. Herein, we discuss how defective epigenetic regulation is involved in the pathogenesis of lupus, which includes both DNA methylation and histone modification changes. (Translational Research 2009;153:4-10)
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