Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
J Leukoc Biol. 2022 May;111(5):1057-1068. doi: 10.1002/JLB.2RU1021-573R. Epub 2022 Feb 21.
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 of 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 the neutrophil life cycle.
中性粒细胞是终末分化的、寿命短的白细胞，对先天免疫至关重要。虽然细胞周期蛋白依赖性激酶（CDKs）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。本综述强调了 CDK 及其伴侣细胞周期蛋白在细胞周期调控之外对中性粒细胞的作用。尽管在不同水平上表达，但 CDK1-10 和几种细胞周期蛋白在中性粒细胞中表达。与 CDK2 特异性抑制或基因缺失相关的观察到的表型表明其在调节中性粒细胞迁移中的作用。CDK4 和 6 调节中性粒细胞胞外陷阱（NETs）的形成，而 CDK5 调节中性粒细胞脱粒。CDK7 和 9 在中性粒细胞凋亡中至关重要，有助于炎症的解决。除了调节成熟中性粒细胞功能的 CDK 外，细胞周期蛋白在造血和粒状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为针对 CDK 治疗以中性粒细胞为主的炎症性疾病和理解中性粒细胞生命周期的调控提供了尚未开发的潜力。
