Human NK Cell Cytoskeletal Dynamics and Cytotoxicity Are Regulated by LIM Kinase
Human NK Cell Cytoskeletal Dynamics and Cytotoxicity Are Regulated by LIM Kinase
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DOI：
10.4049/jimmunol.2000186
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发表时间：
2020-08-01
影响因子：
4.4
通讯作者：
Levy, Bruce D.
中科院分区：
文献类型：
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作者：
Duvall, Melody G.;Fuhlbrigge, Mary E.;Levy, Bruce D.
NK细胞通过其细胞毒性效应功能提供免疫监视和宿主对病毒和肿瘤的保护。细胞骨架重排是NK细胞溶解颗粒运输和免疫突触形成触发靶细胞凋亡的必要条件。LIM激酶（LIMK）通过磷酸化cofilin调控f -肌动蛋白重塑，抑制肌动蛋白断裂和解聚。在这项研究中，在人类NK细胞中，糖皮质激素地塞米松下调了LIMK表达、f -肌动蛋白在免疫突触的积累、溶解颗粒运输和细胞毒性。相反，专门的促分化介质脂素A(4)促进NK细胞LIMK的表达、裂解颗粒向免疫突触的极化和细胞毒性。使用LIMK抑制剂，我们发现LIMK活性对NK细胞的细胞毒性是必要的，包括脂素a(4)的促分解作用。总之，我们的研究结果确定了LIMK是NK细胞细胞骨架重排的重要控制机制，该机制受糖皮质激素和专门的促生介质的差异调节，从而影响NK细胞的细胞毒性。
NK cells provide immune surveillance and host protection against viruses and tumors through their cytotoxic effector function. Cytoskeletal rearrangement is necessary for NK cell lytic granule trafficking and immune synapse formation to trigger apoptosis of targeted cells. LIM kinase (LIMK) regulates F-actin remodeling by phosphorylating cofilin to inhibit actin severing and depolymerization. In this study, in human NK cells, the glucocorticoid dexamethasone downregulated LIMK expression, F-actin accumulation at the immune synapse, lytic granule trafficking, and cytotoxicity. In contrast, the specialized proresolving mediator lipoxin A(4) promoted NK cell LIMK expression, lytic granule polarization to the immune synapse and cytotoxicity. Using a LIMK inhibitor, we show that LIMK activity is necessary for NK cell cytotoxicity, including lipoxin A(4)'s proresolving actions. Together, our findings identify LIMK as an important control mechanism for NK cell cytoskeletal rearrangement that is differentially regulated by glucocorticoids and specialized proresolving mediators to influence NK cell cytotoxicity.