Interferon-α-Enhanced CD100/Plexin-B1/B2 Interactions Promote Natural Killer Cell Functions in Patients with Chronic Hepatitis C Virus Infection.
Interferon-α-Enhanced CD100/Plexin-B1/B2 Interactions Promote Natural Killer Cell Functions in Patients with Chronic Hepatitis C Virus Infection.
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干扰素-α 增强的 CD100/Plexin-B1/B2 相互作用促进慢性丙型肝炎病毒感染患者的自然杀伤细胞功能
DOI：
10.3389/fimmu.2017.01435
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发表时间：
2017
影响因子：
7.3
通讯作者：
Jia Z
中科院分区：
文献类型：
--
作者：
He Y;Guo Y;Fan C;Lei Y;Zhou Y;Zhang M;Ye C;Ji G;Ma L;Lian J;Moorman JP;Yao ZQ;Wang J;Hao C;Zhang Y;Jia Z
CD100，也称为Sema4D，是一种免疫信号素，主要表达在自然杀伤细胞(NK细胞)和T细胞上。CD100作为一种免疫激活分子，通过增强NK细胞与靶细胞之间的相互作用，对NK细胞功能具有重要的免疫调节作用。本研究的目的是研究丙型肝炎病毒感染是否影响CD100的表达，以及干扰素-α治疗是否增强NK杀伤活性以促进丙型肝炎病毒通过CD100清除。采用流式细胞仪检测慢性丙型肝炎患者在接受或不接受聚乙二醇化干扰素-α治疗后NK细胞表面CD10 0的表达。用K562、Huh7.5或HCVJFH-1感染的Huh7.5细胞与NK细胞共同培养，流式细胞仪检测NK细胞的杀伤活性和干扰素-γ的产生。与健康人相比，丙型肝炎病毒感染者的CD100+NK细胞频率受到轻微抑制。干扰素-α治疗可显著上调CD10 0的表达，这一点已被体外培养的外周血单核细胞与表达丙型肝炎病毒的Huh7.5细胞或干扰素-α共培养证实。重要的是，在干扰素-α治疗的早期，丙型肝炎患者NK细胞表面CD100的表达与丙型肝炎病毒核糖核酸水平呈负相关，并且干扰素-α上调的CD100通过与靶细胞上的受体Plexin-B1/B2结合而增强NK杀伤活性。这些结果提示，干扰素-α促进CD100/丛蛋白-B1/B2相互作用在促进慢性丙型肝炎患者NK功能方面起着重要作用。
CD100, also known as Sema4D, is an immune semaphorin constitutively expressed on natural killer (NK) cells and T cells. As an immune activation molecule, CD100 has important immunoregulatory effects on NK functions by enhancing the interactions between NK cells and target cells. The aim of this study was to investigate whether hepatitis C virus (HCV) infection affects CD100 expression, and whether interferon-α treatment enhances NK killing activity to facilitate HCV clearance via CD100. Expression of CD100 on NK cells was evaluated by flow cytometry in patients with chronic HCV infection, with or without pegylated interferon-α-based therapy. NK cell cytotoxicity and interferon (IFN)-γ production were measured by flow cytometry upon culturing the NK cells with K562 and Huh7.5 or HCV JFH-1-infected Huh7.5 cells. The frequency of CD100+ NK cells in HCV-infected individuals was slightly suppressed compared to healthy subjects. IFN-α treatment could significantly upregulate CD100 expression, which was confirmed by in vitro studies using peripheral blood mononuclear cells cocultured with HCV-expressing Huh7.5 cells or IFN-α. Importantly, the expression of CD100 on NK cells from HCV patients was inversely associated with the HCV-RNA levels in the early phase of IFN-α therapy, and the IFN-α upregulated CD100 led to an enhanced NK killing activity through ligations with its receptors plexin-B1/B2 on target cells. These results implied a novel mechanism by which IFN-α enhanced CD100/Plexin-B1/B2 interaction plays an important role in promoting NK functions in patients with chronic hepatitis C.
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影响因子：
15.3
作者：
Crotta, Stefania;Stilla, Annalisa;Wack, Andreas;D'Andrea, Annalisa;Nuti, Sandra;D'Oro, Ugo;Mosca, Marta;Filliponi, Franco;Brunetto, R Maurizia;Bonino, Ferruccio;Abrignani, Sergio;Valiante, Nicholas M
通讯作者：
Valiante, Nicholas M
影响因子：
14.8
作者：
Kato, Takanobu;Date, Tomoko;Wakita, Takaji
通讯作者：
Wakita, Takaji
影响因子：
32.4
作者：
Kumanogoh, A;Watanabe, C;Kikutani, H
通讯作者：
Kikutani, H
影响因子：
20.3
作者：
Fauriat, Cyril;Long, Eric O.;Bryceson, Yenan T.
通讯作者：
Bryceson, Yenan T.
影响因子：
4.4
作者：
Lan, Lin;Gorke, Sebastian;Baumert, Thomas F.
通讯作者：
Baumert, Thomas F.