A curious case of cyclin-dependent kinases in neutrophils.
A curious case of cyclin-dependent kinases in neutrophils.
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DOI：
10.1002/jlb.2ru1021-573r
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发表时间：
2022-05
影响因子：
5.5
通讯作者：
Deng, Qing
中科院分区：
文献类型：
--
作者：
Syahirah, Ramizah;Hsu, Alan Y.;Deng, Qing
中性粒细胞是终末分化的、短命的白细胞，对先天免疫至关重要。虽然细胞周期蛋白依赖性激酶(CDK)通常与细胞周期进程有关，但越来越多的证据表明，它们调节中性粒细胞的基本功能。本文着重介绍CDK及其伙伴细胞周期蛋白在中性粒细胞细胞周期外调节中的作用。CDK1-10和几种细胞周期蛋白在中性粒细胞中表达，尽管表达水平不同。观察到的与CDK2的特异性抑制或基因缺失相关的表型表明，它在调节中性粒细胞迁移方面发挥了作用。CDK4和CDK6调控中性粒细胞胞外陷阱(Net)的形成，而CDK5调控中性粒细胞脱颗粒。CDK7和CDK9在中性粒细胞凋亡中起关键作用，有助于炎症消退。除了调节成熟的中性粒细胞功能的CDK外，细胞周期蛋白在造血和粒细胞生成中也是必不可少的。CDKs在中性粒细胞中的关键作用在靶向CDKs治疗中性粒细胞主导的炎症性疾病和了解中性粒细胞的调节方面具有尚未开发的潜力。
Neutrophils are terminally differentiated, short-lived white blood cells critical for innate immunity. Although cyclin-dependent kinases (CDKs) are typically related to cell cycle progression, increasing evidence has shown that they regulate essential functions of neutrophils. This review highlights the roles of CDKs and their partners, cyclins, in neutrophils, outside cell cycle regulation. CDK1–10 and several cyclins are expressed in neutrophils, albeit at different levels. Observed phenotypes associated with specific inhibition or genetic loss of CDK2 indicate its role in modulating neutrophil migration. CDK4 and 6 regulate neutrophil extracellular traps (NETs) formation, while CDK5 regulates neutrophil degranulation. CDK7 and 9 are critical in neutrophil apoptosis, contributing to inflammation resolution. In addition to the CDKs that regulate mature neutrophil functions, cyclins are essential in hematopoiesis and granulopoiesis. The pivotal roles of CDKs in neutrophils present an untapped potential in targeting CDKs for treating neutrophil-dominant inflammatory diseases and understanding the regulation of neutrophils.