Epigenetic regulation of NK cell differentiation and effector functions.
Epigenetic regulation of NK cell differentiation and effector functions.
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DOI：
10.3389/fimmu.2013.00055
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发表时间：
2013
影响因子：
7.3
通讯作者：
Bryceson YT
中科院分区：
文献类型：
--
作者：
Cichocki F;Miller JS;Anderson SK;Bryceson YT
成熟后，自然杀伤（NK）细胞获得效应子功能和调节受体。新的见解表明，相当大的功能异质性和动态调节的受体表达在成熟的人类NK细胞亚群的基础上不同的发展轴。这些过程包括获得溶解颗粒以及响应于外源性细胞因子刺激或靶细胞相互作用而调节细胞因子产生。一个轴是由自我MHC I类分子的抑制性受体的表达调节，而其他轴是不太明确的，但可能是由不同的激活受体的接合或细胞因子驱动。此外，最近在小鼠中鉴定出能够在二次病毒攻击后迅速扩增和响应的长寿NK细胞亚群，这表明NK细胞分化的编程中存在以前未被认识到的可塑性。在这里，我们回顾了我们的理解成熟NK细胞的发展和可塑性方面的细胞功能的调节进展。此外，我们强调了一些主要的问题，仍然有关的表观遗传变化的基础上的分化和功能的专业化的NK细胞和他们的反应的调节。
Upon maturation, natural killer (NK) cells acquire effector functions and regulatory receptors. New insights suggest a considerable functional heterogeneity and dynamic regulation of receptor expression in mature human NK cell subsets based on different developmental axes. Such processes include acquisition of lytic granules as well as regulation of cytokine production in response to exogenous cytokine stimulation or target cell interactions. One axis is regulated by expression of inhibitory receptors for self-MHC class I molecules, whereas other axes are less well defined but likely are driven by different activating receptor engagements or cytokines. Moreover, the recent identification of long-lived NK cell subsets in mice that are able to expand and respond rapidly following a secondary viral challenge suggest previously unappreciated plasticity in the programming of NK cell differentiation. Here, we review advances in our understanding of mature NK cell development and plasticity with regards to regulation of cellular function. Furthermore, we highlight some of the major questions that remain pertaining to the epigenetic changes that underlie the differentiation and functional specialization of NK cells and the regulation of their responses.