Dynamic DNA methylation patterns across the mouse and human IL10 genes during CD4+ T cell activation; influence of IL-27.
Dynamic DNA methylation patterns across the mouse and human IL10 genes during CD4+ T cell activation; influence of IL-27.
复制标题
DOI：
10.1016/j.molimm.2010.09.009
复制
发表时间：
2010-11
影响因子：
3.6
通讯作者：
Bream JH
中科院分区：
文献类型：
--
作者：
Hedrich CM;Ramakrishnan A;Dabitao D;Wang F;Ranatunga D;Bream JH
IL-10在控制炎症中起关键作用，并且IL-10的抗炎功能基于其从各种细胞来源（最显著的是T细胞）的协调表达来调节。尽管几乎所有的CD 4+亚群都可以表达IL-10，但令人惊讶的是，对控制IL-10诱导的分子机制知之甚少，特别是在人类中。为了研究人IL-10表达的调节，我们建立了hIL-10 BAC转基因小鼠。如前所述，我们观察到髓源性IL-10表达的保守性，但发现人IL-10仅在hIL 10 BAC小鼠脾CD 4 + T细胞中弱表达。由于DNA甲基化是基因表达谱的重要决定因素，我们评估了幼稚和活化的CD 4 + T细胞中人和小鼠IL 10基因的DNA甲基化模式。在小鼠和人IL 10中，在多克隆活化后的幼稚CD 4 + T细胞中没有明显的CpG甲基化模式。然而，总体而言，人IL 10基因具有显著更高水平的DNA甲基化。有趣的是，与IL-10诱导细胞因子IL-27共培养导致小鼠而非人IL-10基因甲基化的位点特异性降低。去甲基化特异性地定位于与已知调控区相邻的内含子位点。我们的研究结果表明，虽然小鼠和人IL-10基因在CD 4 + T细胞活化过程中经历DNA甲基化的可变变化，但IL-27似乎影响特定内含子区域的DNA甲基化，从而与IL-10表达相关。
IL-10 plays a critical role in controlling inflammation and the anti-inflammatory functions of IL-10 are regulated based on its coordinated expression from various cellular sources, most notably T cells. Although nearly all CD4+ subpopulations can express IL-10, surprisingly little is known about the molecular mechanisms which control IL-10 induction, particularly in humans. To examine the regulation of human IL-10 expression, we created the hIL10BAC transgenic mouse. As previously reported, we observed conservation of myeloid-derived IL-10 expression but found that human IL-10 was only weakly expressed in splenic CD4+ T cells from hIL10BAC mice. Since DNA methylation is an important determinant of gene expression profiles, we assessed the patterns of DNA methylation in the human and mouse IL10 genes in naïve and activated CD4+ T cells. Across mouse and human IL10 there were no obvious patterns of CpG methylation in naïve CD4+ T cells following polyclonal activation. Overall however, the human IL10 gene had significantly higher levels of DNA methylation. Interestingly, coculture with the IL-10-inducing cytokine IL-27 lead to a site-specific reduction in methylation of the mouse but not human IL10 gene. Demethylation was specifically localized to an intronic site adjacent to a known regulatory region. Our findings indicate that while the mouse and human IL10 genes undergo variable changes in DNA methylation during CD4+ T cell activation, IL-27 appears to influence DNA methylation in a particular intronic region thus associating with IL-10 expression.
登录
查看更多内容
影响因子：
30.5
作者：
Avni, O;Lee, D;Rao, A
通讯作者：
Rao, A
影响因子：
2.9
作者：
Chen, ZX;Riggs, AD
通讯作者：
Riggs, AD
影响因子：
4.4
作者：
Fields, PE;Kim, ST;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.0708293104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Kim, Sean T.;Fields, Patrick E.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
4.4
作者：
Dong, Jun;Ivascu, Claudia;Thiel, Andreas
通讯作者：
Thiel, Andreas