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
{"title":"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。","authors":"","doi":"10.1016/j.mucimm.2024.07.007","DOIUrl":null,"url":null,"abstract":"<div><div>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 <em>Bmp2</em> and <em>Krt8</em> genes that are associated with AT2-AT1 <em>trans</em>-differentiation, suggesting potential defects in lung repair processes. We identified persistent upregulation of asthma-associated genes, including <em>Il33</em>. EL-RSV-infected mice allergen-challenged exhibited exacerbated allergic response, with significant upregulation of <em>Il33</em> 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 <em>Il33</em> 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.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":null,"pages":null},"PeriodicalIF":7.9000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term alterations in lung epithelial cells after EL-RSV infection exacerbate allergic responses through IL-1β-induced pathways\",\"authors\":\"\",\"doi\":\"10.1016/j.mucimm.2024.07.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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 <em>Bmp2</em> and <em>Krt8</em> genes that are associated with AT2-AT1 <em>trans</em>-differentiation, suggesting potential defects in lung repair processes. We identified persistent upregulation of asthma-associated genes, including <em>Il33</em>. EL-RSV-infected mice allergen-challenged exhibited exacerbated allergic response, with significant upregulation of <em>Il33</em> 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 <em>Il33</em> 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.</div></div>\",\"PeriodicalId\":18877,\"journal\":{\"name\":\"Mucosal Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mucosal Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1933021924000734\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mucosal Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1933021924000734","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信