CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro.
CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro.
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DOI：
10.1016/j.cyto.2012.05.002
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发表时间：
2012-08
期刊：
影响因子：
3.8
通讯作者：
Kelvin DJ
中科院分区：
文献类型：
--
作者：
Sidahmed AM;León AJ;Bosinger SE;Banner D;Danesh A;Cameron MJ;Kelvin DJ
CXCL 10在人T淋巴细胞凋亡和存活方面的作用。③对参与该过程的信号通路进行了研究。关于CXCL 10在病毒感染中的作用的新观点。CXCL 10是干扰素刺激基因组的一部分，在不同的病毒感染中通过诱导细胞活化、趋化和淋巴细胞向Th 1表型的启动而发挥重要作用。在这项研究中，我们在体外研究了CXCL 10在活化的人原代T淋巴细胞凋亡或存活方面的作用，并描绘了所涉及的信号通路。CXCL 10与IL-2和/或IFNα联合诱导T淋巴细胞凋亡。此外，CXCL 10诱导的CXCR 3活化也触发了可被百日咳毒素阻断的促存活信号。对下游信号激酶的分析表明，凋亡是p38 MAPK依赖的，促存活信号依赖于PI 3 K的持续激活和Akt的瞬时激活。另一方面，p44/p42 ERK的瞬时激活对T淋巴细胞存活没有影响。我们提出了一个免疫模型，其中CXCL 10，连同其他共刺激细胞因子，参与T淋巴细胞的活化，促进某些淋巴细胞亚群的存活和扩增，并诱导对感染组织的趋化性。另一方面，CXCL 10可能有助于触发其他T淋巴细胞亚群的凋亡，包括那些短暂激活但后来缺乏适当的特异性共刺激信号以确保其存活的淋巴细胞。
► Effects of CXCL10 in human T lymphocytes in terms of apoptosis and survival. ► The signaling pathways that are involved in the process were studied. ► New perspective about the role of CXCL10 during viral infections. CXCL10 is part of the group of interferon-stimulated genes and it plays an important role during different viral infections by inducing cell activation, chemotaxis and lymphocyte priming toward the Th1 phenotype. In this study, we investigated in vitro the effects of CXCL10 in activated human primary T lymphocytes in terms of apoptosis or survival, and delineated the signaling pathways that are involved. CXCL10, in combination with IL-2 and/or IFNα, induces apoptosis in T lymphocytes. Moreover, CXCL10-induced activation of CXCR3 also triggers pro-survival signals that can be blocked by pertussis toxin. The analysis of the downstream signaling kinases shows that apoptosis is p38 MAPK-dependent and the pro-survival signals rely on the sustained activation of PI3K and the transient activation of Akt. On the other hand, the transient activation of p44/p42 ERK did not have an impact on T lymphocyte survival. We propose an immunological model in which CXCL10, together with other co-stimulating cytokines, participates in the activation of T lymphocytes, promotes survival and expansion of certain lymphocyte subsets, and induces chemotaxis toward the infected tissues. On the other hand, CXCL10 might contribute to the triggering of apoptosis in other subsets of T lymphocytes, including those lymphocytes that were transiently activated but later lacked the appropriate sets of specific co-stimulating signals to ensure their survival.
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影响因子：
3.7
作者：
Rowe T;León AJ;Crevar CJ;Carter DM;Xu L;Ran L;Fang Y;Cameron CM;Cameron MJ;Banner D;Ng DC;Ran R;Weirback HK;Wiley CA;Kelvin DJ;Ross TM
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作者：
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