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Review
. 2025 Jan;19(1):29-41.
doi: 10.1080/17476348.2024.2449079. Epub 2025 Jan 6.

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

Allan R Brasier  1   2
Affiliations
Review

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

Allan R Brasier. Expert Rev Respir Med. 2025 Jan.

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.

Keywords: Allergic asthma; epithelial barrier; epithelial plasticity; hexosamine biosynthesis; innate inflammation; unfolded protein response.

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Conflict of interest statement

Declarations of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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