Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI 48109, United States.
Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI 48109, United States.
Clin Immunol. 2018 Nov;196:97-102. doi: 10.1016/j.clim.2018.04.003. Epub 2018 Apr 11.
Patients with active lupus have altered T cells characterized by low DNA methyltransferase levels. We hypothesized that low DNA methyltransferase levels synergize with low methionine levels to cause greater overexpression of genes normally suppressed by DNA methylation. CD4+ T cells from lupus patients and controls were stimulated with PHA then cultured in custom media with normal or low methionine levels. Oxidative stress was induced by treating the normal CD4+ T cells with peroxynitrite prior to culture. Methylation sensitive gene expression was measured by flow cytometry. Results showed low methionine levels caused greater overexpression of methylation sensitive genes in peroxynitrite treated T cells relative to untreated T cells, and in T cells from lupus patients relative to T cells from healthy controls. In conclusion, low dietary transmethylation micronutrient levels and low DNA methyltransferase levels caused either by oxidative stress or lupus, have additive effects on methylation sensitive T cell gene expression.
患有活动性狼疮的患者具有特征为 DNA 甲基转移酶水平降低的改变的 T 细胞。我们假设，低 DNA 甲基转移酶水平与低蛋氨酸水平协同作用，导致通常受 DNA 甲基化抑制的基因过度表达。来自狼疮患者和对照者的 CD4+T 细胞用 PHA 刺激，然后在含有正常或低蛋氨酸水平的定制培养基中培养。在培养之前，用过氧化亚硝酰处理正常 CD4+T 细胞以诱导氧化应激。通过流式细胞术测量甲基化敏感基因的表达。结果表明，低蛋氨酸水平导致经过氧化亚硝酰处理的 T 细胞相对于未处理的 T 细胞以及狼疮患者的 T 细胞相对于健康对照者的 T 细胞中，甲基化敏感基因的过度表达更大。总之，低膳食转甲基微量营养素水平和由氧化应激或狼疮引起的低 DNA 甲基转移酶水平对甲基化敏感的 T 细胞基因表达具有相加作用。
