CD40L demethylation in CD4 + T cells from women with rheumatoid arthritis

CD40L demethylation in CD4 + T cells from women with rheumatoid arthritis
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DOI:
10.1016/j.clim.2012.07.006
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发表时间:
2012-10-01
影响因子:
8.6
通讯作者:
Lu, Q.
Lu, Q.
中科院分区:
医学3区
文献类型:
--
作者:
Liao, J.;Liang, G.;Lu, Q.

文献摘要

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我们之前已经证明,X染色体上CD40L的DNA去甲基化是女性对系统性红斑狼疮(SLE)易感性的原因。目前尚不清楚CD40L基因的异常甲基化是否也导致女性类风湿关节炎(RA)的高发病率。在这项研究中,我们使用实时RT-PCR和流式细胞术来比较CD40L的表达水平,并使用亚硫酸酯测序来评估CD40L启动子区域的甲基化状态。结果显示,女性RA患者CD4(+) T细胞中CD40L表达上调。此外,在女性RA患者的CD4(+) T细胞中发现CD40L启动子区域被去甲基化,这与CD40L mRNA表达增加相对应。这些发现表明,DNA去甲基化有助于RA CD4(+) T细胞中CD40L的表达,并可能部分解释这种疾病在女性中的优势。(c) 2012 Elsevier Inc.版权所有。
We have previously demonstrated that DNA demethylation of CD40L on the X chromosome is responsible for female susceptibility to systemic lupus erythematosus (SLE). It is unknown whether aberrant methylation of the CD40L gene also contributes to the higher incidence of rheumatoid arthritis (RA) in females. In this study, we used real-time RT-PCR and flow cytometry to compare CD40L expression levels, and bisulfite sequencing to assess the methylation status of the CD40L promoter region. The results show that CD40L is upregrulated in CD4(+) T cells of female patients with RA. In addition, the CD40L promoter region in CD4(+) T cells from female RA patients was found to be demethylated, which corresponded with increased CD40L mRNA expression. These findings suggest that DNA demethylation contributes to CD40L expression in RA CD4(+) T cells and may in part explain the female preponderance of this disease. (c) 2012 Elsevier Inc. All rights reserved.