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上皮-间质可塑性、屏障功能障碍与固有免疫途径之间的相互作用塑造了过敏性气道疾病的发生发展。

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

作者信息

Brasier Allan R

机构信息

School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.

The Institute for Clinical and Translational Research, Madison, WI, USA.

出版信息

Expert Rev Respir Med. 2025 Jan;19(1):29-41. doi: 10.1080/17476348.2024.2449079. Epub 2025 Jan 6.

DOI:10.1080/17476348.2024.2449079
PMID:39745473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11757041/
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 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.

摘要

引言

在具有遗传易感性的个体中，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）。在此过程中，下呼吸道前哨细胞中激活的模式识别受体（PRR）会发出上皮损伤修复信号通路，导致细胞状态改变[上皮间质可塑性（EMP）]、屏障破坏和致敏。

涵盖领域

  1. 支气管肺泡连接处前哨上皮细胞的特征；2. 空气过敏原对上皮PRR的影响；3. 紧密连接（TJ）在屏障功能中的作用以及空气过敏原如何破坏其功能；4. 黏膜转化生长因子自分泌环的诱导激活2型固有淋巴细胞（ICL2）导致Th2极化；5. 呼吸道合胞病毒（RSV）如何导致杯状细胞增生；6. 内质网（ER）应激与代谢适应的耦合以及对重塑的影响。

专家观点

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固有免疫时，正常的屏障功能会被破坏，从而促进慢性炎症和Th2反应。对激活的PRR如何诱导EMP与TJ破坏、代谢重编程和细胞外基质沉积之间关系的更深入机制理解，为恢复AA中的屏障功能、减少致敏和重塑提供了新的经过生物学验证的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/d7d748501a08/nihms-2045484-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/16860bee3efa/nihms-2045484-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/2ee1421e9a1f/nihms-2045484-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/f1b2ce4704e6/nihms-2045484-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/4370b5e2329b/nihms-2045484-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/d7d748501a08/nihms-2045484-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/16860bee3efa/nihms-2045484-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/2ee1421e9a1f/nihms-2045484-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/f1b2ce4704e6/nihms-2045484-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/4370b5e2329b/nihms-2045484-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b5a/11757041/d7d748501a08/nihms-2045484-f0005.jpg

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Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity.
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