New concepts in the pathogenesis of drug-induced lupus.

Although the importance of DNA methylation in normal cellular development and hereditary disease states has been appreciated for some time, the role of environmental agents in causing DNA methylation abnormalities and the effects of DNA hypomethylation on T cells have only recently been examined. This review summarizes current knowledge about the role of DNA methylation in regulating T function and gene expression and highlights a novel mechanism causing autoimmunity, in which epigenetic modification of T cell DNA by environmental agents plays an important role in triggering lupus-like diseases. The observations that DNA methylation inhibitors modify gene expression and induce autoreactivity in cloned, Ag-specific CD4+ cells in vitro, that the modified cells cause autoimmunity in vivo, and that similar changes are found in patients with active lupus provide a new approach to understanding how some forms of autoimmunity develop and may lead to new and more effective treatments.