IκB Kinase β Is Required for Activation of NF-κB and AP-1 in CD3/CD28-Stimulated Primary CD4+ T Cells
IκB Kinase β Is Required for Activation of NF-κB and AP-1 in CD3/CD28-Stimulated Primary CD4+ T Cells
复制标题
DOI：
10.4049/jimmunol.1102938
复制
发表时间：
2012-03-15
影响因子：
4.4
通讯作者：
Piccinini, Marco
中科院分区：
文献类型：
--
作者：
Lupino, Elisa;Ramondetti, Cristina;Piccinini, Marco
TCR 和 CD28 辅助受体通过各自的配体结合，激活信号转导级联，最终导致转录因子 NFAT、AP-1 和 NF-κ B 的激活，这些因子是细胞因子表达和 T 细胞克隆扩增所必需的。先前的研究表明，在成熟的T细胞中，AP-1和NF-kappa B的激活依赖于蛋白激酶C theta，这表明存在共同的信号通路。在这项研究中，我们发现，在人原代CD4(+) T细胞中，暴露于细胞渗透性IKK β抑制剂PS-1145或IKK β基因消除会消除细胞增殖，并损害响应CD3和CD28辅助受体结合的NF-κB和AP-1转录因子的激活。此外，我们发现，在缺乏 IKK β 活性的情况下刺激 T 细胞会促进 T 细胞信号传导负调节因子的时间依赖性和环孢菌素敏感性表达，从而导致 T 细胞的低反应状态。免疫学杂志，2012，188：2545-2555。
Engagement of the TCR and CD28 coreceptor by their respective ligands activates signal transduction cascades that ultimately lead to the activation of the transcription factors NFAT, AP-1, and NF-kappa B, which are required for the expression of cytokines and T cell clonal expansion. Previous studies have demonstrated that in mature T cells, activation of AP-1 and NF-kappa B is dependent on protein kinase C theta, suggesting the existence of a common signaling pathway. In this study, we show that in human primary CD4(+) T cells, exposure to the cell-permeable IKK beta inhibitor PS-1145 or genetic ablation of IKK beta abrogates cell proliferation and impairs the activation of NF-kappa B and AP-1 transcription factors in response to engagement of CD3 and CD28 coreceptor. In addition, we show that stimulation of T cells in the absence of IKK beta activity promotes the time-dependent and cyclosporine-sensitive expression of negative regulators of T cell signaling leading to a hyporesponsive state of T cells. The Journal of Immunology, 2012, 188: 2545-2555.