Signaling for synergistic activation of natural killer cells.
Signaling for synergistic activation of natural killer cells.
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DOI：
10.4110/in.2012.12.6.240
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发表时间：
2012-12
期刊：
影响因子：
6
通讯作者：
Kim HS
中科院分区：
文献类型：
--
作者：
Kwon HJ;Kim HS
自然杀伤（NK）细胞在病毒感染和细胞转化的早期监测中发挥关键作用，并通过其直接裂解靶细胞和细胞因子分泌的效应功能参与炎症反应的控制。NK细胞对靶细胞的激活是由各种激活和抑制受体传递的信号的净平衡决定的。NK细胞活化的一个显著特征是，单个激活受体单独刺激静止NK细胞不能产生自然的细胞毒性。相反，需要特定的共激活受体对通过协同依赖机制释放NK细胞激活。由于每个共激活受体使用不同的信号模块，NK细胞的协同作用依赖于这些不同信号的整合。这就解释了为什么研究NK细胞协同作用的机制是重要和必要的。最近的研究表明，NK细胞的协同作用依赖于聚合在一个关键检查点元件的互补信号的整合，而不是简单地放大单个信号来克服内在激活阈值。本文就NK细胞活化过程中的信号事件及NK细胞协同作用的研究进展作一综述。
Natural killer (NK) cells play a pivotal role in early surveillance against virus infection and cellular transformation, and are also implicated in the control of inflammatory response through their effector functions of direct lysis of target cells and cytokine secretion. NK cell activation toward target cell is determined by the net balance of signals transmitted from diverse activating and inhibitory receptors. A distinct feature of NK cell activation is that stimulation of resting NK cells with single activating receptor on its own cannot mount natural cytotoxicity. Instead, specific pairs of co-activation receptors are required to unleash NK cell activation via synergy-dependent mechanism. Because each co-activation receptor uses distinct signaling modules, NK cell synergy relies on the integration of such disparate signals. This explains why the study of the mechanism underlying NK cell synergy is important and necessary. Recent studies revealed that NK cell synergy depends on the integration of complementary signals converged at a critical checkpoint element but not on simple amplification of the individual signaling to overcome intrinsic activation threshold. This review focuses on the signaling events during NK cells activation and recent advances in the study of NK cell synergy.