IL-22 Is Essential for Lung Epithelial Repair following Influenza Infection
IL-22 Is Essential for Lung Epithelial Repair following Influenza Infection
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DOI：
10.1016/j.ajpath.2012.12.007
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发表时间：
2013-04-01
影响因子：
6
通讯作者：
Alcorn, John F.
中科院分区：
文献类型：
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作者：
Pociask, Derek A.;Scheller, Erich V.;Alcorn, John F.
流感感染在美国和全世界都很普遍。尽管感染导致的死亡率很低，但发病率很常见，并且对恢复中涉及的分子事件知之甚少。流感感染导致持续的远端肺重塑，其机制尚不清楚。最近发现IL-22介导上皮修复。我们认为IL-22对流感病毒感染后肺功能和结构的恢复至关重要。用甲型流感PR 8/34 H1N1感染野生型和IL-22（-/-）小鼠，并在感染后随访长达21天。IL-22受体定位于幼稚小鼠的气道上皮，但在流感感染诱导的肺实质重塑部位表达。与野生型小鼠相比，IL-22（-/-）小鼠表现出加重的肺损伤，这与感染后21天肺功能降低相关。在野生型小鼠中观察到上皮化生，但在以纤维化表型增加为特征的IL-22（-/-）动物中不明显。基因表达分析显示，在其他几个生物过程的变化中，参与修复过程的上皮基因的异常表达。这些数据表明，IL-22是流感感染后正常肺修复所必需的。IL-22是间质性肺疾病的一种新途径。
Influenza infection is widespread in the United States and the world. Despite Low mortality rates due to infection, morbidity is common and Little is known about the molecular events involved in recovery. Influenza infection results in persistent distal lung remodeling, and the mechanism (s) involved are poorly understood. Recently IL-22 has been found to mediate epithelial repair. We propose that IL-22 is critical for recovery of normal lung function and architecture after influenza infection. Wild-type and IL-22(-/-) mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22(-/-) mice displayed exacerbated Lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. Epithelial metaplasia was observed in wild-type mice but was not evident in IL-22(-/-) animals that were characterized with an increased fibrotic phenotype. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes, among changes in several other biological processes. These data indicate that IL-22 is required for normal lung repair after influenza infection. IL-22 represents a novel pathway involved in interstitial lung disease.