Role of T Cell DNA Methylation in Lupus Syndromes
Role of T Cell DNA Methylation in Lupus Syndromes
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DOI：
10.1177/096120339400300611
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发表时间：
1994-12
期刊：
影响因子：
2.6
通讯作者：
R. Yung;B. Richardson
中科院分区：
文献类型：
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作者：
R. Yung;B. Richardson
目前的理论假设，暴露于某些环境因素会诱发狼疮遗传易感个体。然而，环境因素与免疫系统相互作用引发狼疮的机制尚不清楚。最近的研究表明，一些与狼疮相关的环境因子，如普鲁卡因胺、肼嗪和紫外线，会抑制T细胞DNA甲基化，增加LFA-1的表达并诱导自身反应性。此外，从活动性狼疮患者中分离的T细胞具有低甲基化的DNA， DNA甲基转移酶活性降低，并且在自发裂解自体巨噬细胞的自反应性细胞亚群上过度表达LFA-1。最近的研究表明，小鼠T细胞的过继转移与DNA甲基化抑制剂产生自身反应，足以在其他健康的同基因受体中引起狼疮样疾病。总之，这些结果支持了一种新的自身免疫模型，其中某些环境因子通过抑制DNA甲基化和改变某些基因的表达来修饰T细胞，从而诱导自身反应性。这些自身反应性细胞随后与宿主相互作用，产生类似狼疮的疾病。
Current theories postulate that exposure to certain environmental agents will induce lupus in genetically predisposed individuals. However, the mechanisms by which environmental agents interact with the immune system to trigger lupus is unclear. Recent work has shown that some environmental agents associated with lupus, such as procainamide, hydralazine and ultraviolet light, will inhibit T cell DNA methylation, increase LFA-1 expression and induce autoreactivity. In addition, T cells isolated from patients with active lupus have hypomethylated DNA, diminished DNA methyltransferase activity and overexpress LFA-1 on an autoreactive subset of cells which spontaneously lyses autologous macrophages. More recent work has shown that the adoptive transfer of murine T cells made autoreactive with DNA methylation inhibitors is sufficient to cause a lupus-like disease in otherwise healthy syngeneic recipients. Together, these results support a new model of autoimmunity, in which certain environmental agents modify T cells by inhibiting DNA methylation and altering expression of certain genes, thereby inducing autoreactivity. The autoreactive cells then interact with the host to produce a lupus-like disease.