Polycomb chromobox (Cbx) 7 modulates activation-induced CD4+ T cell apoptosis
Polycomb chromobox (Cbx) 7 modulates activation-induced CD4+ T cell apoptosis
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Polycomb chromobox (Cbx) 7 调节激活诱导的 CD4( ) T 细胞凋亡。
DOI：
10.1016/j.abb.2014.10.004
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发表时间：
2014-12-15
影响因子：
3.9
通讯作者：
Xu, Jin
中科院分区：
文献类型：
--
作者：
Li, Jian;Li, Yang;Xu, Jin
CD 4（+）T细胞极化在许多免疫疾病中起关键作用;其发病机制尚不清楚。染色体盒同源物7（Cbx 7）参与几种细胞类型的基因转录。本研究旨在探讨Cbx 7调节CD 4（+）T细胞极化的机制。通过定量RT-PCR和Western blotting评估Cbx 7的表达。流式细胞仪检测CD 4 + T细胞凋亡情况。采用甲基化特异性PCR检测FasL基因启动子甲基化。结果表明，CD 4（+）CD 25（-）T细胞经抗CD 3/CD 28抗体激活后表达Cbx 7显著增加，而特异性抗原则抑制了Cbx 7的表达。Cbx 7基因敲低的CD 4（+）T细胞中检测到更多的凋亡细胞。暴露于胰岛素样生长因子-1上调CD 4（+）T细胞中Cbx 7的表达。在抗原特异性TCR活化后，Cbx 7缺陷型CD 4（+）T细胞表达更多的FasL，并显示FasL基因启动子高去甲基化比野生型CD 4（+）T细胞。此外，Cbx 7过表达的CD 4（+）T细胞显示FasL基因启动子去甲基化水平较低。我们的结论是，CD 4（+）T细胞表达Cbx 7，后者阻止FasL的表达和激活诱导的CD 4（+）T细胞凋亡。(C)2014爱思唯尔公司All rights reserved.
CD4(+) T cell polarization plays a critical role in a number of immune disorders; the pathogenesis is unclear. Chromobox homolog 7 (Cbx7) is involved in the gene transcription of several cell types. This study aims to investigate the mechanism by which Cbx7 modulates the CD4(+) T cell polarization. Expression of Cbx7 was assessed by quantitative RT-PCR and Western blotting. Apoptosis of CD4(+) T cell was analyzed by flow cytometry. The FasL promoter methylation was evaluated by the methylation specific PCR. The results showed that CD4(+) CD25(-) T cells express Cbx7 that was increased significantly after activation by exposing to anti-CD3/CD28 Ab, but suppressed by exposing to specific antigens. More apoptotic cells were detected in CD4(+) T cells with the Cbx7 gene knockdown. Exposure to insulin-like growth factor-1 up regulated the expression of Cbx7 in CD4(+) T cells. After antigen-specific TCR activation, Cbx7-deficient CD4(+) T cells expressed more FasL and showed the FasL gene promoter hyper demethylation than wild CD4(+) T cells. In addition, CD4(+) T cells with overexpression of Cbx7 showed lower levels of FasL gene promoter demethylation. We conclude that CD4(+) T cells express Cbx7; the latter prevents FasL expression and the activation-induced CD4(+) T cell apoptosis. (C) 2014 Elsevier Inc. All rights reserved.