Controlling natural killer cell responses: integration of signals for activation and inhibition.

Controlling natural killer cell responses: integration of signals for activation and inhibition.
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DOI:
10.1146/annurev-immunol-020711-075005
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发表时间:
2013
影响因子:
29.7
通讯作者:
Rajagopalan S
Rajagopalan S
中科院分区:
医学1区
文献类型:
--
作者:
Long EO;Kim HS;Liu D;Peterson ME;Rajagopalan S

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在缺乏抗原特异性受体的情况下,如何整合信号来控制NK细胞的反应一直是一个挑战,但最近的工作揭示了一些控制NK细胞反应的潜在原理。NK细胞使用一系列天生的受体来感知它们的环境,并对感染、细胞压力和转化引起的变化做出反应。没有单一的激活受体占主导地位;相反,来自多种受体组合的协同信号被整合起来,以激活自然的细胞毒性和细胞因子的产生。MHC-I类抑制性受体在控制NK细胞反应中起着关键作用,矛盾的是,在维持NK细胞对后续激活事件的应答状态中,这一过程被称为许可。MHC-I特异性抑制受体既可以阻断激活信号,也可以触发信号来磷酸化和失活小接头Crk。抑制信号的这些不同方面被结合到一个可撤销的许可证模型中,以可逆地调整NK细胞的反应性。
Understanding how signals are integrated to control NK cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for MHC class I have a critical role in controlling NK cell responses and paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibitory signaling are incorporated into a revocable license model for the reversible tuning of NK cell responsiveness.
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