Yung R L, Johnson K J, Richardson B C
Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
Lab Invest. 1995 Dec;73(6):746-59.
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.
尽管DNA甲基化在正常细胞发育和遗传性疾病状态中的重要性已被认识一段时间了，但环境因素在导致DNA甲基化异常中的作用以及DNA低甲基化对T细胞的影响直到最近才被研究。这篇综述总结了目前关于DNA甲基化在调节T细胞功能和基因表达中作用的知识，并强调了一种导致自身免疫的新机制，其中环境因素对T细胞DNA的表观遗传修饰在引发狼疮样疾病中起重要作用。DNA甲基化抑制剂在体外可改变克隆的、抗原特异性CD4+细胞中的基因表达并诱导自身反应性，这些修饰细胞在体内可导致自身免疫，且在活动性狼疮患者中发现了类似变化，这些观察结果为理解某些形式的自身免疫如何发生提供了新方法，并可能带来新的、更有效的治疗手段。
