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Am J Pathol:IL-22在流感病毒感染后肺组织修复中起重要作用

来源:生物谷 2013-03-13 21:33

2013年3月7日 讯 /生物谷BIOON/ --一旦流感过去了,流感的慢性影响往往会被忽视。一项新的研究结果表明,细胞因子白细胞介素22(IL-22)在流感病毒感染中正常肺组织的修复中起着至关重要的作用。这项研究发表在2013年4月出版的American Journal of Pathology杂志上。

随着感染日益流行和/或更多流感毒株的出现,了解病毒对宿主上皮细胞的影响和肺修复过程是非常重要的。这一新研究发现为能开发出促进流感病毒感染后正常肺组织功能和体系结构的恢复,减少继发感染的新治疗剂的可能性。

新研究的一个关键发现是,即使感染发生后,流感导致的肺实质重塑也可能是引发肺进一步损伤的至关重要步骤。这一系列实验用6-8周龄野生型(WT)小鼠(C57BL/6品系)以及IL-22缺陷小鼠完成,这些小鼠感染H1N1 A型流感PR/8/34或对照媒介物。

为了分析IL-22在肺中的分布,免疫组化检测了IL-22Ra1受体的表达情况。调查发现野生型小鼠没有受流感病毒感染,IL-22受体分布在大,小的气道上皮细胞中,但在软细胞组织中不分布。

他们指出,此受体的分布表明,在肺损伤的情况下,IL-22主要与支气管上皮细胞相互作用。流感病毒感染后21天,IL-22受体能在受伤区域观察到,如处于修复阶段的肺泡中。研究证实了IL-22受体在流感有关的损伤部位中上调。

研究人员还报告说,流感病毒感染后10天,IL-22缺陷小鼠表现出比WT对照组更严重的损害和肺水肿,高乳酸脱氢酶水平和支气管肺泡灌洗液中总蛋白含量显著上升。更严重的肺损伤的另一个指示是IL-22-缺陷动物中淋巴细胞的数目增加,功能也出现了障碍。

流感病毒感染21日后组织学检查表明,与野生型小鼠相比,IL-22缺陷小鼠显示区域的弥漫性炎症,肺泡损伤,内膜增厚更严重,蛋白质的积累,胶原沉积增加。基因表达分析显示,体内缺乏IL-22的小鼠肺修复过程中上皮细胞有关的基因异常表达。

IL-22在促进上皮修复的作用正在逐渐显现。IL-22在流感病毒感染过程中调节肺上皮的修复反应发挥了关键作用,IL-22是目前正在开发的一种潜在治疗药物。(生物谷:Bioon.com)

IL-22 Is Essential for Lung Epithelial Repair following Influenza Infection

Derek A. Pociask, et al.

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.

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