EL-RSV感染后肺上皮细胞的长期改变通过IL-1β诱导途径加剧过敏反应运行标题:EL-RSV 和长期改变。

IF 7.9 2区 医学 Q1 IMMUNOLOGY
Susan B. Morris , Ramon Ocadiz-Ruiz , Nobuhiro Asai , Carrie-Anne Malinczak , Andrew J Rasky , Grace K. Lombardo , Evan M. Velarde , Catherine Ptaschinski , Rachel L Zemans , Nicholas W. Lukacs , Wendy Fonseca
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引用次数: 0

摘要

生命早期(EL)呼吸道感染会增加肺部疾病风险,尤其是与哮喘有关的EL-呼吸道合胞病毒(EL-RSV)感染。哮喘易感性的机制仍不清楚。在本研究中,我们研究了 EL-RSV 感染四周后对肺部的长期影响。我们发现肺上皮细胞发生了改变,肺泡2型上皮细胞(AT2)的比例上升,AT1和AT2-AT1亚群细胞的比例下降,与AT2-AT1跨分化相关的Bmp2和Krt8基因上调,这表明肺修复过程存在潜在缺陷。我们发现了哮喘相关基因(包括 Il33)的持续上调。EL-RSV 感染的小鼠在过敏原挑战下表现出加剧的过敏反应,肺部和 AT2 细胞中的 Il33 显著上调。在暴露于 EL-IL-1β 的小鼠中也观察到了类似的长期效应。值得注意的是,在急性EL-RSV感染期间用IL-1ra治疗可减轻肺泡的长期改变和过敏原加重的反应。最后,在 EL-RSV 组和 EL-IL1β 组收获的 AT2 细胞中检测到了 Il33 基因启动子的表观遗传修饰,这表明 RSV 感染后上皮细胞的长期改变依赖于 IL-1β 途径。这项研究有助于深入了解 RSV 感染后哮喘易感性的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Long-term alterations in lung epithelial cells after EL-RSV infection exacerbate allergic responses through IL-1β-induced pathways
Early-life (EL) respiratory infections increase pulmonary disease risk, especially EL-Respiratory Syncytial Virus (EL-RSV) infections linked to asthma. Mechanisms underlying asthma predisposition remain unknown. In this study, we examined the long-term effects on the lung after four weeks post EL-RSV infection. We identified alterations in the lung epithelial cell, with a rise in the percentage of alveolar type 2 epithelial cells (AT2) and a decreased percentage of cells in the AT1 and AT2-AT1 subclusters, as well as upregulation of Bmp2 and Krt8 genes that are associated with AT2-AT1 trans-differentiation, suggesting potential defects in lung repair processes. We identified persistent upregulation of asthma-associated genes, including Il33. EL-RSV-infected mice allergen-challenged exhibited exacerbated allergic response, with significant upregulation of Il33 in the lung and AT2 cells. Similar long-term effects were observed in mice exposed to EL-IL-1β. Notably, treatment with IL-1ra during acute EL-RSV infection mitigated the long-term alveolar alterations and the allergen-exacerbated response. Finally, epigenetic modifications in the promoter of the Il33 gene were detected in AT2 cells harvested from EL-RSV and EL-IL1β groups, suggesting that long-term alteration in the epithelium after RSV infection is dependent on the IL-1β pathway. This study provides insight into the molecular mechanisms of asthma predisposition after RSV infection.
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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