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Oxidative stress and dietary micronutrient deficiencies contribute to overexpression of epigenetically regulated genes by lupus T cells
Clinical Immunology ( IF 8.6 ) Pub Date : 2018-04-11 , DOI: 10.1016/j.clim.2018.04.003
Donna Ray , Faith M. Strickland , Bruce C. Richardson

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.



中文翻译:

氧化应激和饮食中微量营养素缺乏导致狼疮T细胞过表达表观遗传调控基因

活动性狼疮患者的T细胞已改变,其特征是DNA甲基转移酶水平低。我们假设低的DNA甲基转移酶水平与低的蛋氨酸水平协同作用,从而引起通常被DNA甲基化抑制的基因更大的过表达。用PHA刺激狼疮患者和对照组的CD4 + T细胞,然后在蛋氨酸水平正常或较低的常规培养基中培养。通过在培养前用过亚硝酸盐处理正常的CD4 + T细胞来诱导氧化应激。通过流式细胞术测量甲基化敏感性基因表达。结果表明,相对于未处理的T细胞,低甲硫氨酸水平导致过氧亚硝酸盐处理的T细胞和狼疮患者的T细胞中甲基化敏感基因的过量过表达相对于健康对照组的T细胞。综上所述,

更新日期:2018-04-11
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