白细胞介素-25 阻断增强呼吸道病毒感染期间的抗病毒免疫。
IL-25 blockade augments antiviral immunity during respiratory virus infection.
机构信息
The University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia.
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia.
出版信息
Commun Biol. 2022 May 4;5(1):415. doi: 10.1038/s42003-022-03367-z.
IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal antibody (LNR125) revealed a re-calibrated response defined by increased type I/III IFN and reduced expression of type-2 immune genes CCL26, IL1RL1 and IL-25 receptor. LNR125 treatment also increased type I/III IFN expression by coronavirus infected BECs. Exogenous IL-25 treatment increased viral load with suppressed innate immunity. In vivo LNR125 treatment reduced IL-25/type 2 cytokine expression and increased IFN-β expression and reduced lung viral load. We define a new immune-regulatory role for IL-25 that directly inhibits virus induced airway epithelial cell innate anti-viral immunity.
IL-25 参与病毒诱发的哮喘恶化发病机制。然而，IL-25 对抗病毒免疫的影响仍有待阐明。我们观察到未感染的气道上皮细胞顶表面有大量的 IL-25 和 IL-25 受体表达，鼻病毒感染增加了 IL-25 的表达。对用抗 IL-25 单克隆抗体（LNR125）处理的感染鼻病毒的分化哮喘支气管上皮细胞（BEC）的免疫转录组进行分析，揭示了一种由 I 型/III 型 IFN 增加和 2 型免疫基因 CCL26、IL1RL1 和 IL-25 受体表达减少定义的重新校准反应。LNR125 治疗还增加了受冠状病毒感染的 BEC 中 I 型/III 型 IFN 的表达。外源性 IL-25 处理增加了病毒载量，同时抑制了先天免疫。体内 LNR125 治疗减少了 IL-25/2 型细胞因子的表达，增加了 IFN-β 的表达，并减少了肺部病毒载量。我们定义了 IL-25 的一个新的免疫调节作用，它直接抑制病毒诱导的气道上皮细胞先天抗病毒免疫。
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