Involvement of NK Cells in IL-28B-Mediated Immunity against Influenza Virus Infection
Involvement of NK Cells in IL-28B-Mediated Immunity against Influenza Virus Infection
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NK 细胞参与 IL-28B 介导的流感病毒感染免疫
DOI：
10.4049/jimmunol.1601430
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发表时间：
2017-08-01
影响因子：
4.4
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
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作者：
Wang, Yanshi;Li, Tingting;Tian, Zhigang
IL-28B是新发现的III型干扰素家族成员之一，与其他家族成员相比具有独特的抗病毒特性。NK细胞在抵御病毒方面发挥着重要作用，但对IL-28B在NK细胞功能中的作用知之甚少。在甲型流感病毒(小鼠适应型流感A/PR/8/34株)感染的小鼠模型中，肝细胞特异性基因传递诱导的IL-28B的长期过表达在NK细胞存在的情况下具有很强的抗病毒作用。IL-28B高表达野生型小鼠脾、肝、肺NK细胞百分率和绝对数明显增加，CD11b和CD27或CD11b和KLRG1表型染色显示NK细胞增殖加快，成熟加快。此外，IL-28B对NK细胞的作用依赖于巨噬细胞，这在体外共培养实验和体内巨噬细胞或肺泡巨噬细胞耗竭实验中得到了证实。Transwell研究表明，CFSE标记的NK细胞的增殖是由IL-28B刺激的肺泡巨噬细胞分泌的未知可溶性因子(S)以剂量依赖的方式驱动的，而不需要细胞与细胞的直接接触。了解IL-28B促进NK细胞的功能将有助于该细胞因子的临床应用。
IL-28B is a member of the newly discovered type III IFN family and exhibits unique antiviral properties compared with other family members. NK cells play a critical role in defending against viruses; however, little is known about the role of IL-28B in NK cell function. In a mouse model of influenza A virus (mouse adapted influenza A/PR/8/34 strain) infection, long-term overexpression of IL-28B induced by hepatocyte-specific gene delivery exerted a strong antiviral effect in the presence of NK cells. In IL-28B-overexpressing wild-type mice, the percentages and absolute numbers of NK cells in the spleen, liver, and lung were markedly increased, with higher proliferation and accelerated NK cell maturation based on phenotypes staining with CD11b and CD27 or CD11b and KLRG1. Furthermore, the effect of IL-28B on NK cells was macrophage dependent, as confirmed in an in vitro coculture assay and in in vivo macrophage- or alveolar macrophage-depletion experiments. Transwell studies demonstrated that CFSE-labeled NK cell proliferation was driven, in a dose-dependent manner, by unknown soluble factor(s) secreted by IL-28B-stimulated alveolar macrophages, without requiring direct cell-cell contact. An understanding of the NK cell-promoting features of IL-28B will facilitate future clinical application of this cytokine.