Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection.
Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection.
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在流感病毒感染过程中，第2组IL-5的先天淋巴样细胞的产生受NKT细胞的调节。
DOI：
10.1371/journal.ppat.1003615
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发表时间：
2013-09
期刊：
影响因子：
6.7
通讯作者：
Braciale TJ
中科院分区：
文献类型：
--
作者：
Gorski SA;Hahn YS;Braciale TJ
呼吸道病毒感染，例如流感，通常诱导强烈的I型（促炎细胞因子）免疫应答，然而，已经观察到2型细胞因子的产生。呼吸道病毒感染期间2型细胞因子的产生与哮喘恶化有关;然而，2型细胞因子也可能是组织保护性的。白细胞介素（IL）-5是一种典型的2型细胞因子，对嗜酸性粒细胞成熟和排出骨髓至关重要。然而，对呼吸道病毒感染过程中IL-5产生的细胞来源和潜在的细胞和分子基础的调节知之甚少。使用流感病毒感染的小鼠模型，我们发现IL-5向感染的气道中的强瞬时释放沿着嗜酸性粒细胞向肺中的显著和进行性积累，特别是在感染的恢复期，即病毒清除后。IL-5的细胞来源是浸润感染肺的第2组先天性淋巴样细胞（ILC 2）。有趣的是，病毒清除后嗜酸性粒细胞的进行性积累反映在产生ILC 2的c-kit+ IL-5的快速扩增中。我们进一步证明了在恢复期间ILC 2产生IL-5的能力增强与ILC 2表达IL-33受体亚基ST 2的增强是相伴的。最后，我们表明，NKT细胞，以及肺泡巨噬细胞（AM），是内源性来源的IL-33，增强IL-5的生产从ILC 2。总的来说，这些结果揭示了c-kit+ ILC 2与产生IL-33的NKT和AM的相互作用导致ILC 2大量产生IL-5，并解释了在流感感染的恢复期期间观察到的嗜酸性粒细胞的积累。IL-5是一种细胞因子，通常与寄生虫感染和过敏反应有关。IL-5的主要作用被认为是促进先天免疫细胞类型嗜酸性粒细胞的发育和成熟，嗜酸性粒细胞也是过敏性疾病如哮喘的罪魁祸首。在呼吸道病毒感染期间，例如流感感染，IL-5和嗜酸性粒细胞被认为在宿主防御中不起主要作用。在这里，我们表明，IL-5的产生是响应于流感感染，并导致嗜酸性粒细胞在肺中的进行性积累。我们表明，一种新发现的细胞类型，第2组先天淋巴样细胞（ILC 2），是负责在流感感染过程中产生IL-5和ILC 2的能力，使IL-5大大增加病毒清除后，即在恢复阶段。在流感感染的恢复期，ILC 2产生IL-5部分受NKT细胞和该细胞类型产生的IL-33调节。
Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine) immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may also be tissue protective. Interleukin (IL)-5 is a prototypical type 2 cytokine that is essential for eosinophil maturation and egress out of the bone marrow. However, little is known about the cellular source and underlying cellular and molecular basis for the regulation of IL-5 production during respiratory virus infection. Using a mouse model of influenza virus infection, we found a robust transient release of IL-5 into infected airways along with a significant and progressive accumulation of eosinophils into the lungs, particularly during the recovery phase of infection, i.e. following virus clearance. The cellular source of the IL-5 was group 2 innate lymphoid cells (ILC2) infiltrating the infected lungs. Interestingly, the progressive accumulation of eosinophils following virus clearance is reflected in the rapid expansion of c-kit+ IL-5 producing ILC2. We further demonstrate that the enhanced capacity for IL-5 production by ILC2 during recovery is concomitant with the enhanced expression of the IL-33 receptor subunit, ST2, by ILC2. Lastly, we show that NKT cells, as well as alveolar macrophages (AM), are endogenous sources of IL-33 that enhance IL-5 production from ILC2. Collectively, these results reveal that c-kit+ ILC2 interaction with IL-33 producing NKT and AM leads to abundant production of IL-5 by ILC2 and accounts for the accumulation of eosinophils observed during the recovery phase of influenza infection. IL-5 is a cytokine that is typically associated with parasitic infections and allergic reactions. The primary role of IL-5 is thought to be for the development and maturation of an innate immune cell type, the eosinophil, which is also a culprit in allergic diseases such as asthma. During respiratory virus infection, such as influenza infection, IL-5 and eosinophils are not thought to play a major role in host defense. Here we show that IL-5 is produced in response to influenza infection and results in the progressive accumulation of eosinophils in the lung. We show that a newly discovered cell type, the group 2 innate lymphoid cell (ILC2), is responsible for IL-5 production during influenza infection and that the capacity of ILC2 to make IL-5 is greatly increased following virus clearance, i.e. during the recovery phase. The production of IL-5 by ILC2 is in part regulated by NKT cells and IL-33 produced by this cell type during the recovery phase of influenza infection.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
DOI：
10.4049/jimmunol.1200571
发表时间：
2013-01-01
期刊：
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DOI：
10.1084/jem.20101850
发表时间：
2011-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hufford MM;Kim TS;Sun J;Braciale TJ
通讯作者：
Braciale TJ
影响因子：
82.9
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影响因子：
4.4
作者：
Al-Garawi, Amal A.;Fattouh, Ramzi;Jordana, Manel
通讯作者：
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