Interactions Between Epithelial Mesenchymal Plasticity, Barrier Dysfunction and Innate Immune Pathways Shape the Genesis of Allergic Airway Disease

Overview

Journal Expert Rev Respir Med

Specialty Pulmonary Medicine

Date 2025 Jan 2

PMID 39745473

Authors

Allan R Brasier

Affiliations

Soon will be listed here.

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.

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