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α2β1 整合素是病毒感染期间 NK 细胞最佳增殖所必需的,但对于获得效应功能或 NK 细胞介导的病毒控制则并非如此。

α2β1 Integrin Is Required for Optimal NK Cell Proliferation during Viral Infection but Not for Acquisition of Effector Functions or NK Cell-Mediated Virus Control.

机构信息

Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107.

Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107

出版信息

J Immunol. 2020 Mar 15;204(6):1582-1591. doi: 10.4049/jimmunol.1900927. Epub 2020 Feb 3.

Abstract

NK cells play an important role in antiviral resistance. The integrin α2, which dimerizes with integrin β1, distinguishes NK cells from innate lymphoid cells 1 and other leukocytes. Despite its use as an NK cell marker, little is known about the role of α2β1 in NK cell biology. In this study, we show that in mice α2β1 deficiency does not alter the balance of NK cell/ innate lymphoid cell 1 generation and slightly decreases the number of NK cells in the bone marrow and spleen without affecting NK cell maturation. NK cells deficient in α2β1 had no impairment at entering or distributing within the draining lymph node of ectromelia virus (ECTV)-infected mice or at becoming effectors but proliferated poorly in response to ECTV and did not increase in numbers following infection with mouse CMV (MCMV). Still, α2β1-deficient NK cells efficiently protected from lethal mousepox and controlled MCMV titers in the spleen. Thus, α2β1 is required for optimal NK cell proliferation but is dispensable for protection against ECTV and MCMV, two well-established models of viral infection in which NK cells are known to be important.

摘要

自然杀伤 (NK) 细胞在抗病毒抵抗中发挥着重要作用。整合素 α2 与整合素 β1 二聚化,将 NK 细胞与先天淋巴细胞 1 和其他白细胞区分开来。尽管它被用作 NK 细胞标志物,但对于 α2β1 在 NK 细胞生物学中的作用知之甚少。在这项研究中,我们表明在小鼠中,α2β1 缺陷不会改变 NK 细胞/先天淋巴细胞 1 生成的平衡,仅略微减少骨髓和脾脏中的 NK 细胞数量,而不影响 NK 细胞成熟。缺乏 α2β1 的 NK 细胞在进入或分布于感染单纯疱疹病毒(ECTV)的小鼠引流淋巴结或成为效应细胞方面没有受损,但对 ECTV 的增殖能力较差,并且在感染小鼠 CMV(MCMV)后数量不会增加。尽管如此,α2β1 缺陷型 NK 细胞仍能有效预防致死性小鼠痘和控制 MCMV 在脾脏中的滴度。因此,α2β1 是 NK 细胞最佳增殖所必需的,但对于预防 ECTV 和 MCMV 感染是可有可无的,这两种病毒感染模型是 NK 细胞发挥重要作用的既定模型。

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