T cells and ILC2s are major effector cells in influenza-induced exacerbation of allergic airway inflammation in mice.

T cells and ILC2s are major effector cells in influenza-induced exacerbation of allergic airway inflammation in mice.
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DOI:
10.1002/eji.201747421
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发表时间:
2019-01
影响因子:
5.4
通讯作者:
Hendriks RW
Hendriks RW
中科院分区:
医学3区
文献类型:
--
作者:
Li BWS;de Bruijn MJW;Lukkes M;van Nimwegen M;Bergen IM;KleinJan A;GeurtsvanKessel CH;Andeweg A;Rimmelzwaan GF;Hendriks RW

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流感病毒感染是严重哮喘急性发作的重要原因,但目前尚不清楚Th 1介导的抗病毒反应如何触发典型的Th 2疾病。我们研究了流感病毒感染小鼠中的CD 4 + T细胞和第2组先天淋巴细胞(ILC 2)。我们发现流感病毒感染后ILC 2在肺中迅速积累,但IL-5和IL-13分泌的诱导延迟,并伴随着T细胞活化。在流感诱导的过敏性气道炎症加重模型中,我们注意到与单独的慢性屋尘螨(HDM)介导的气道炎症相比,支气管肺泡灌洗中ILC 2数量和细胞因子产生最初减少。ILC 2s表型的特征在于低T1/ST 2、ICOS、KLRG 1和CD 25表达,类似于幼稚ILC 2。ILC 2对流感诱导急性加重早期2型细胞因子产生的贡献有限。相比之下,当暴露于HDM和流感病毒时,T细胞显示IL-4和IL-5的产生增加。在病毒清除后,ILC 2恢复了活化的T1/ST 2 highICOShighKLRG 1highCD 25 high表型,与细胞因子产生配对,并且是2型细胞因子环境的主要贡献者。总的来说,我们的数据表明T细胞和ILC 2都有助于流感引起的过敏性气道炎症的恶化,但具有不同的动力学。
Influenza virus infection is an important cause of severe asthma exacerbations, but it remains unclear how a Th1‐mediated antiviral response triggers a prototypical Th2 disease. We investigated CD4+ T cells and group 2 innate lymphoid cells (ILC2s) in influenza virus‐infected mice. We found that ILC2s accumulated in the lung rapidly after influenza virus infection, but the induction of IL‐5 and IL‐13 secretion was delayed and concomitant with T cell activation. In an influenza‐induced exacerbation of allergic airway inflammation model we noticed an initial reduction of ILC2 numbers and cytokine production in broncho‐alveolar lavage compared to chronic house dust mite (HDM)‐mediated airway inflammation alone. ILC2s phenotype was characterized by low T1/ST2, ICOS, KLRG1, and CD25 expression, resembling naïve ILC2s. The contribution of ILC2s to type 2 cytokine production in the early stage of the influenza‐induced exacerbation was limited. In contrast, T cells showed increased IL‐4 and IL‐5 production when exposed to both HDM and influenza virus. Upon virus clearance, ILC2s regained an activated T1/ST2highICOShighKLRG1highCD25high phenotype paired with cytokine production and were major contributors to the type 2 cytokine milieu. Collectively, our data indicate that both T cells and ILC2s contribute to influenza‐induced exacerbation of allergic airway inflammation, but with different kinetics.
树突状细胞对于维持流感病毒感染小鼠肺部的三级淋巴结构至关重要。
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