Induction and maintenance of IL-4 expression are regulated differently by the 3' enhancer in CD4 T cells.
Induction and maintenance of IL-4 expression are regulated differently by the 3' enhancer in CD4 T cells.
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DOI：
10.4049/jimmunol.1003353
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Chang CH
中科院分区：
文献类型：
--
作者：
Sofi MH;Qiao Y;Ansel KM;Kubo M;Chang CH
已知当 CD4 T 细胞分化为 Th2 细胞而非 Th1 细胞时，IL-4 表达会在 CD4 T 细胞中被激活。然而，由表达 MH II 类胸腺细胞选择的 CD4 T 细胞，称为胸腺细胞选择 CD4 T 细胞（T-CD4 T 细胞），在 Th1 和 Th2 条件下都表达 IL-4。在这项研究中，我们研究了 T-CD4 T 细胞中 IL-4 基因表达调节的分子机制。我们发现 T-CD4 T 细胞在胸腺中选择后不久就表达 IL-4。 IL-4 基因 3' 增强子区域的 DNase I 超敏 (HS) 位点 HS5a 和 HS5 缺陷会减少 IL-4 的产生，但 T-CD4 T 细胞能够在 Th1 诱导条件下产生 IL-4。与此一致的是，在不存在与 HS5 相互作用的重组信号结合蛋白-J 的情况下，IL-4 在 Th1 分化的 T-CD4 T 细胞中表达。当使用报告系统将 HS5 与其他内源性调控元件分开检查时，胸腺上皮细胞选择的 CD4 T 细胞不能单独使用 HS5 转录 IL-4 报告基因。然而，HS5能够诱导T-CD4 T细胞中IL-4报告基因的表达。有趣的是，Th1 分化信号导致 IL-4 内源基因 HS5 脱乙酰化，而 Th2 诱导环境则没有影响。因此，在T-CD4 T细胞中，HS5在IL-4表达的诱导期发挥着至关重要的作用，但Th1细胞中IL-4表达的维持需要额外的调控元件。
IL-4 expression is known to be activated in CD4 T cells when they are differentiated to Th2 but not Th1 cells. However, CD4 T cells selected by MH class II-expressing thymocytes, named thymocyte-selected CD4 T cells (T-CD4 T cells), express IL-4 under both Th1 and Th2 conditions. In this study, we investigated molecular mechanisms by which IL-4 gene expression is regulated in T-CD4 T cells. We found that T-CD4 T cells express IL-4 soon after selection in the thymus. Deficiency of DNase I hypersensitive (HS) sites HS5a and HS5 at the 3′-enhancer region in the IL-4 gene decreased IL-4 production, but T-CD4 T cells were able to make IL-4 under the Th1-inducing condition. Consistent with this, IL-4 was expressed in Th1 differentiated T-CD4 T cells in the absence of recombination signal binding protein-J that interacts with HS5. When HS5 was examined separately from other endogenous regulatory elements using a reporter system, CD4 T cells that are selected by thymic epithelial cells cannot transcribe the IL-4 reporter gene with HS5 alone. However, HS5 was able to induce the expression of the IL-4 reporter gene in T-CD4 T cells. Interestingly, the Th1 differentiating signal led to deacetylation at HS5 of the IL-4 endogenous gene, whereas the Th2-inducing environment had no effect. Therefore, in T-CD4 T cells, HS5 plays an essential role during the induction phase of IL-4 expression, but the maintenance of IL-4 expression in Th1 cells requires additional regulatory elements.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Li, Wei;Sofi, M. Hanief;Chang, Cheong-Hee
通讯作者：
Chang, Cheong-Hee
影响因子：
20.3
作者：
Markert, ML;Alexieff, MJ;Skinner, MA
通讯作者：
Skinner, MA
影响因子：
32.4
作者：
Choi, EY;Jung, KC;Park, SH
通讯作者：
Park, SH
DOI：
10.1073/pnas.1332805100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Matsuda, JL;Gapin, L;Kronenberg, M
通讯作者：
Kronenberg, M