• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Medical Genomics >A global transcriptional view of apoptosis in human T-cell activation
【24h】

A global transcriptional view of apoptosis in human T-cell activation

机译：人类T细胞活化中细胞凋亡的整体转录观点

获取原文
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background T-cell activation is an essential step of immune response. The process of proper T-cell activation is strictly monitored and regulated by apoptosis signaling. Yet, regulation of apoptosis, an integral and crucial facet during the process of T-cell activation, is not well understood. Methods In this study, a Gene-Ontology driven global gene expression analysis coupled with protein abundance and activity assays identified genes and pathways associated with regulation of apoptosis in primary human CD3+ T cells and separately CD4+ and CD8+ T cells. Results We identified significantly regulated apoptotic genes in several protein families, such as BCL2 proteins, CASPASE proteins, and TNF receptors, and detailed their transcriptional kinetics during the T-cell activation process. Transcriptional patterns of a few select genes (BCL2A1, BBC3 and CASP3) were validated at the protein level. Many of these apoptotic genes are involved in NF-κB signaling pathway, including TNFRSF10A, TNFRSF10B, TRAF4, TRAF1, TRAF3, and TRAF6. Upregulation of NF-κB and IκB family genes (REL, RELA, and RELB, NFKBIA, NFKBIE and NFKB1) at 48 to 96 hours, supported by the increase of phosphorylated RELA (p65), suggests that the involvement of the NF-κB complex in the process of T-cell proliferation is not only regulated at the protein level but also at the transcriptional level. Examination of genes involved in MAP kinase signalling pathway, important in apoptosis, suggests an induction of p38 and ERK1 cascades in T-cell proliferation (at 48 to 96 hours), which was explored using phosphorylation assays for p38 (MAPK14) and ERK1 (MAPK3). An immediate and short-lived increase of AP-1 activity measured by DNA-binding activity suggests a rapid and transient activation of p38 and/or JNK cascades upon T-cell activation. Conclusion This comparative genome-scale, transcriptional analysis of T-cell activation in the CD4+ and CD8+ subsets and the mixed CD3+ population identified many apoptosis genes not previously identified in the context of T-cell activation. Furthermore, it provided a comprehensive temporal analysis of the transcriptional program of apoptosis associated with T-cell activation.
机译：背景T细胞活化是免疫反应的重要步骤。适当的T细胞活化过程受到凋亡信号的严格监控和调节。然而，关于细胞凋亡的调节是T细胞活化过程中不可或缺的重要方面，目前尚不清楚。方法在这项研究中，由基因本体论驱动的全局基因表达分析与蛋白质丰度和活性分析相结合，鉴定了与人类原代CD3 + T细胞以及CD4 +和CD8 + T细胞凋亡调控相关的基因和途径。结果我们在几个蛋白家族中鉴定出受调节的凋亡基因，例如BCL2蛋白，CASPASE蛋白和TNF受体，并详细介绍了它们在T细胞活化过程中的转录动力学。在蛋白质水平上验证了一些选择基因（BCL2A1，BBC3和CASP3）的转录模式。这些凋亡基因中有许多与NF-κB信号通路有关，包括TNFRSF10A，TNFRSF10B，TRAF4，TRAF1，TRAF3和TRAF6。 NF-κB和IκB家族基因（REL，RELA和RELB，NFKBIA，NFKBIE和NFKB1）的上调在48至96小时受到磷酸化RELA（p65）的增加的支持，表明NF-κB复合体的参与在T细胞增殖过程中，不仅在蛋白质水平受到调控，而且在转录水平也受到调控。对参与细胞凋亡重要的MAP激酶信号通路的基因的研究表明，在T细胞增殖（在48到96小时）中诱导了p38和ERK1级联反应，这是通过对p38（MAPK14）和ERK1（MAPK3 ）。通过DNA结合活性测得的AP-1活性立即且短暂增加，表明T细胞活化后p38和/或JNK级联反应迅速而短暂地活化。结论这项比较基因组规模的CD4 +和CD8 +子集以及混合CD3 +群体中T细胞活化的转录分析确定了许多以前在T细胞活化过程中未发现的凋亡基因。此外，它提供了与T细胞活化相关的凋亡转录程序的全面时间分析。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号