Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus.

Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus.
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DOI:
10.1155/2010/931018
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发表时间:
2010
影响因子:
--
通讯作者:
Lu Q
Lu Q
中科院分区:
其他
文献类型:
--
作者:
Zhao M;Tang J;Gao F;Wu X;Liang Y;Yin H;Lu Q

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IL-10和IL-13在系统性红斑狼疮(SLE)患者Th2细胞分化和自身抗体产生中起重要作用。然而,导致SLE患者IL10和IL13过度表达的机制尚不清楚。在这项研究中,我们证实了SLE患者CD4+T细胞中IL10和IL13mRNA水平以及血清IL10和IL13蛋白水平均升高。我们发现SLE患者外周血中IL-10和IL-13基因调控区的DNA甲基化水平较健康对照组降低,且与IL-10和IL-13的表达呈负相关。此外,用去甲基化试剂5-氮杂胞苷(5-azaC)处理健康的CD4+T细胞可增加IL-10和IL-13的转录。综上所述,我们的结果表明启动子甲基化是CD4+T细胞IL10和IL13表达的决定因素,我们认为DNA低甲基化导致SLE患者IL10和IL13的过度表达。
Interleukin- (IL-)10 and IL-13 play important roles in Th2 cell differentiation and production of autoantibodies in patients with (SLE). However, the mechanisms leading to IL10 and IL13 overexpression in SLE patients are not well understood. In this study, we confirm that the levels of both IL10 and IL13 mRNA in CD4+ T cells and of serum IL10 and IL13 proteins are increased in SLE patients. We show that the DNA methylation levels within IL10 and IL13 gene regulatory domains are reduced in SLE CD4+ T cells relative to healthy controls and negatively correlate with IL10 and IL13 mRNA expression. Moreover, treating healthy CD4+ T cells with the demethylating agent 5-azacytidine (5-azaC) increased IL10 and IL13 mRNA transcription. Together, our results show that promoter methylation is a determinant of IL10 and IL13 expression in CD4+ T cells, and we propose that DNA hypomethylation leads to IL10 and IL13 overexpression in SLE patients.
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发表时间: 2010-05-01
影响因子: --
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