Dipak R Patel1, Bruce C Richardson. 1. University of Michigan, Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA.
Abstract
PURPOSE OF REVIEW: Epigenetic mechanisms regulate gene expression, and epigenetic gene dysregulation is implicated in the pathogenesis of a growing number of disorders. Of the autoimmune diseases, epigenetic mechanisms are most clearly involved in human systemic lupus erythematosus (SLE). Herein, we summarize earlier work on epigenetic mechanisms contributing to human SLE. We first focus on the roles of DNA demethylation and DNA methyltransferase enzyme dysregulation, and we then review recent and important advances in this field. RECENT FINDINGS: Many advances in the past year have been made. The importance of DNA demethylation in SLE was confirmed through twin studies. New T lymphocyte immune genes that are activated by DNA demethylation, and that may participate in autoreactivity, were identified. Finally, novel mechanisms contributing to DNA demethylation in SLE were discovered. SUMMARY: A comprehensive understanding of the epigenetic mechanisms contributing to SLE will likely enable development of new therapeutic agents and strategies that target the dysregulated genes or correct the aberrant epigenetic modifications. Although specific agents have not yet been tested in SLE, the studies reviewed hold promise that these approaches will be useful in the treatment of human lupus.
PURPOSE OF REVIEW: Epigenetic mechanisms regulate gene expression, and epigenetic gene dysregulation is implicated in the pathogenesis of a growing number of disorders. Of the autoimmune diseases, epigenetic mechanisms are most clearly involved in humansystemic lupus erythematosus (SLE). Herein, we summarize earlier work on epigenetic mechanisms contributing to humanSLE. We first focus on the roles of DNA demethylation and DNA methyltransferase enzyme dysregulation, and we then review recent and important advances in this field. RECENT FINDINGS: Many advances in the past year have been made. The importance of DNA demethylation in SLE was confirmed through twin studies. New T lymphocyte immune genes that are activated by DNA demethylation, and that may participate in autoreactivity, were identified. Finally, novel mechanisms contributing to DNA demethylation in SLE were discovered. SUMMARY: A comprehensive understanding of the epigenetic mechanisms contributing to SLE will likely enable development of new therapeutic agents and strategies that target the dysregulated genes or correct the aberrant epigenetic modifications. Although specific agents have not yet been tested in SLE, the studies reviewed hold promise that these approaches will be useful in the treatment of human lupus.
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