title: Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies against a series of nuclear antigens. Although the exact cause of SLE is still unknown, the influence of environment, which is largely reflected by the epigenetic mechanisms, with DNA methylation changes in particular, are generally considered as key players in the pathogenesis of SLE. As an important post-translational modification, DNA methylation mainly suppresses the expression of relevant genes. Accumulating evidence has indicated that abnormal DNA hypomethylation in T cells is an important epigenetic hallmark in SLE. Apart from those classic methylation-sensitive autoimmunity-related genes in lupus, such as CD11a (ITGAL), Perforin (PRF1), CD70 (TNFSF7), CD40 ligand (TNFSF5) and PP2Acα, the genome-wide methylation pattern has also been explored recently, providing us a more and more full-scale picture of the abnormal status of DNA methylation in SLE. On the other hand, certain miRNAs, RFX1, defective ERK pathway signaling, Gadd45α and DNA hydroxymethylation have been proposed as potential mechanisms leading to DNA hypomethylation in lupus. In this review, we summarize current understanding of T cell DNA methylation changes and the consequently altered gene expressions in lupus, and how they contribute to the development of SLE. Possible mechanisms underlying these aberrancies are also discussed based on the reported literature and our own findings.
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenetics, Changsha, Hunan 410011, PR China.
authors: Yiqun
authors: Y
authors: Zhang
authors: Ming
authors: M
authors: Zhao
authors: Amr H
authors: AH
authors: Sawalha
authors: Bruce
authors: B
authors: Richardson
authors: Qianjin
authors: Q
authors: Lu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019175:DNA Methylation / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D035683:MicroRNAs / Q000235:genetics; D008957:Models, Genetic; D018448:Models, Immunological
chemical_list: D035683:MicroRNAs