Interactions between epithelial mesenchymal plasticity, barrier dysfunction and innate immune pathways shape the genesis of allergic airway disease.

Expert review of respiratory medicine Pub Date : 2025-01-01 Epub Date: 2025-01-06 DOI:10.1080/17476348.2024.2449079
Allan R Brasier
{"title":"Interactions between epithelial mesenchymal plasticity, barrier dysfunction and innate immune pathways shape the genesis of allergic airway disease.","authors":"Allan R Brasier","doi":"10.1080/17476348.2024.2449079","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>In genetically predisposed individuals, exposure to aeroallergens and infections from RNA viruses shape epithelial barrier function, leading to Allergic Asthma (AA). Here, activated pattern recognition receptors (PRRs) in lower airway sentinel cells signal epithelial injury-repair pathways leading to cell-state changes [epithelial mesenchymal plasticity (EMP)], barrier disruption and sensitization.</p><p><strong>Areas covered: </strong>1. Characteristics of sentinel epithelial cells of the bronchoalveolar junction, 2. The effect of aeroallergens on epithelial PRRs, 3. Role of tight junctions (TJs) in barrier function and how aeroallergens disrupt their function, 4. Induction of mucosal TGF autocrine loops activating type-2 innate lymphoid cells (ICL2s) leading to Th2 polarization, 5. How respiratory syncytial virus (RSV) directs goblet cell hyperplasia, and 6. Coupling of endoplasmic reticulum (ER) stress to metabolic adaptations and effects on <i>basal lamina</i> remodeling.</p><p><strong>Expert opinion: </strong>When aeroallergens or viral infections activate innate immunity in sentinel cells of the bronchoalveolar junction, normal barrier function is disrupted, promoting chronic inflammation and Th2 responses. An improved mechanistic understanding of how activated PRRs induce EMP couples with TJ disruption, metabolic reprogramming and ECM deposition provides new biologically validated targets to restore barrier function, reduce sensitization, and remodeling in AA.</p>","PeriodicalId":94007,"journal":{"name":"Expert review of respiratory medicine","volume":" ","pages":"29-41"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757041/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert review of respiratory medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17476348.2024.2449079","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/6 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: In genetically predisposed individuals, exposure to aeroallergens and infections from RNA viruses shape epithelial barrier function, leading to Allergic Asthma (AA). Here, activated pattern recognition receptors (PRRs) in lower airway sentinel cells signal epithelial injury-repair pathways leading to cell-state changes [epithelial mesenchymal plasticity (EMP)], barrier disruption and sensitization.

Areas covered: 1. Characteristics of sentinel epithelial cells of the bronchoalveolar junction, 2. The effect of aeroallergens on epithelial PRRs, 3. Role of tight junctions (TJs) in barrier function and how aeroallergens disrupt their function, 4. Induction of mucosal TGF autocrine loops activating type-2 innate lymphoid cells (ICL2s) leading to Th2 polarization, 5. How respiratory syncytial virus (RSV) directs goblet cell hyperplasia, and 6. Coupling of endoplasmic reticulum (ER) stress to metabolic adaptations and effects on basal lamina remodeling.

Expert opinion: When aeroallergens or viral infections activate innate immunity in sentinel cells of the bronchoalveolar junction, normal barrier function is disrupted, promoting chronic inflammation and Th2 responses. An improved mechanistic understanding of how activated PRRs induce EMP couples with TJ disruption, metabolic reprogramming and ECM deposition provides new biologically validated targets to restore barrier function, reduce sensitization, and remodeling in AA.

上皮间充质可塑性、屏障功能障碍和先天免疫途径之间的相互作用形成了过敏性气道疾病的发生。
在遗传易感个体中,暴露于空气过敏原和RNA病毒感染会影响上皮屏障功能,导致过敏性哮喘(AA)。在这里,下气道前哨细胞中激活的模式识别受体(PRRs)向上皮损伤修复途径发出信号,导致细胞状态改变[上皮间充质可塑性(epithelial mesenchymal plasticity, EMP)]、屏障破坏和致敏。覆盖范围:1;支气管肺泡交界处前哨上皮细胞的特征2. 空气过敏原对上皮PRRs的影响3. 紧密连接(TJs)在屏障功能中的作用及空气过敏原如何破坏其功能4. 诱导粘膜TGF β自分泌环激活2型先天淋巴样细胞(ICL2s)导致Th2极化;5. 呼吸道合胞病毒(RSV)如何引导杯状细胞增生6. 内质网应激与代谢适应的耦合及其对基底膜重塑的影响。专家意见:当空气过敏原或病毒感染激活支气管肺泡连接处前哨细胞的先天免疫时,正常屏障功能被破坏,促进慢性炎症和Th2反应。对活化的PRRs如何诱导EMP与TJ破坏、代谢重编程和ECM沉积耦合的机制的进一步了解,为恢复屏障功能、减少AA的致敏和重塑提供了新的生物学验证靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
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