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蛋白激酶 CK2 调控感染过程中 CD8 T 细胞效应器和记忆功能。

Protein Kinase CK2 Controls CD8 T Cell Effector and Memory Function during Infection.

机构信息

Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL; and.

Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.

出版信息

J Immunol. 2022 Sep 1;209(5):896-906. doi: 10.4049/jimmunol.2101080. Epub 2022 Aug 1.

Abstract

Protein kinase CK2 is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α') and two regulatory subunits (CK2β). CK2 promotes cancer progression by activating the NF-κB, PI3K/AKT/mTOR, and JAK/STAT pathways, and also is critical for immune cell development and function. The potential involvement of CK2 in CD8 T cell function has not been explored. We demonstrate that CK2 protein levels and kinase activity are enhanced upon mouse CD8 T cell activation. CK2α deficiency results in impaired CD8 T cell activation and proliferation upon TCR stimulation. Furthermore, CK2α is involved in CD8 T cell metabolic reprogramming through regulating the AKT/mTOR pathway. Lastly, using a mouse infection model, we demonstrate that CK2α is required for CD8 T cell expansion, maintenance, and effector function in both primary and memory immune responses. Collectively, our study implicates CK2α as an important regulator of mouse CD8 T cell activation, metabolic reprogramming, and differentiation both in vitro and in vivo.

摘要

蛋白激酶 CK2 是一种丝氨酸/苏氨酸激酶,由两个催化亚基(CK2α 和/或 CK2α')和两个调节亚基(CK2β)组成。CK2 通过激活 NF-κB、PI3K/AKT/mTOR 和 JAK/STAT 途径促进癌症进展,对于免疫细胞的发育和功能也至关重要。CK2 是否参与 CD8 T 细胞功能尚未得到探索。我们证明,在小鼠 CD8 T 细胞激活时,CK2 蛋白水平和激酶活性增强。在 TCR 刺激下,CK2α 缺乏会导致 CD8 T 细胞激活和增殖受损。此外,CK2α 通过调节 AKT/mTOR 通路参与 CD8 T 细胞代谢重编程。最后,我们使用小鼠 感染模型证明,在原发性和记忆性免疫反应中,CK2α 对于 CD8 T 细胞的扩增、维持和效应功能都是必需的。综上所述,我们的研究表明 CK2α 是体外和体内调节小鼠 CD8 T 细胞激活、代谢重编程和分化的重要调节因子。

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