DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus.
DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus.
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DOI：
10.3109/08916934.2013.826207
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发表时间：
2014-06
期刊：
影响因子：
3.5
通讯作者：
Renaudineau Y
中科院分区：
文献类型：
--
作者：
Fali T;Le Dantec C;Thabet Y;Jousse S;Hanrotel C;Youinou P;Brooks WH;Perl A;Renaudineau Y
系统性红斑狼疮（SLE）疾病是一种病因不明的自身免疫性疾病，主要影响育龄妇女。由于先前的研究，包括我们的研究，已经表明，从SLE患者的CD 4 + T细胞和B细胞是在其能力的缺陷，甲基化其DNA抗原刺激后，本研究的目的是调查是否DNA去甲基化影响HRES-1在B细胞的转录。HRES-1是在SLE中过表达的人内源性逆转录病毒（HERV）的原型。我们已经观察到SLE B细胞的特征在于它们不能甲基化HRES-1启动子，无论是在未刺激的还是在抗IgM刺激的B细胞中。反过来，在B细胞受体结合后，SLE B细胞中HRES-1/p28表达增加，但在对照组中没有。在SLE B细胞中，Erk/DNMT 1通路存在缺陷。此外，用抗IL-6受体单克隆抗体阻断SLE B细胞中IL-6的自分泌环恢复了DNA甲基化，并且HRES-1/p28表达的控制变得有效。因此，更好地了解SLE中HERV失调加强了我们对疾病的理解，并开辟了新的治疗前景。
Systemic lupus erythematosus (SLE) disease is an autoimmune disease of unknown aetiology that affects predominantly women of child bearing age. Since previous studies, including ours, have demonstrated that CD4+ T cells and B cells from SLE patients are defective in their ability to methylate their DNA upon antigen stimulation, the aim of this study was to investigate whether DNA demethylation affects the transcription of HRES-1 in B cells. HRES-1 is the prototype of Human Endogenous Retrovirus (HERV) overexpressed in SLE. We have observed that SLE B cells were characterized by their incapacity to methylate the HRES-1 promoter, both in unstimulated and in anti-IgM stimulated B cells. In turn, HRES-1/p28 expression was increased in SLE B cells after B cell receptor engagement, but not in controls. In SLE B cells the Erk/DNMT1 pathway was defective. In addition, blocking the autocrine-loop of IL-6 in SLE B cells with an anti-IL-6 receptor monoclonal antibody restores DNA methylation and control of HRES-1/p28 expression became effective. As a consequence, a better understanding of HERV dysregulation in SLE reinforces our comprehension of the disease and opens new therapeutic perspectives.
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影响因子：
--
作者：
Li, Yaping;Zhao, Ming;Lu, Qianjin
通讯作者：
Lu, Qianjin
DOI：
10.1073/pnas.89.5.1939
发表时间：
1992-03-01
影响因子：
11.1
作者：
BANKI, K;MACEDA, J;PERL, A
通讯作者：
PERL, A
影响因子：
12.3
作者：
Hernando, Henar;Shannon-Lowe, Claire;Ballestar, Esteban
通讯作者：
Ballestar, Esteban
影响因子：
5.5
作者：
Balada, Eva;Ordi-Ros, Josep;Vilardell-Tarres, MiqLjel
通讯作者：
Vilardell-Tarres, MiqLjel
影响因子：
3.2
作者：
Magistrelli, C;Samoilova, E;Perl, A
通讯作者：
Perl, A