Airway epithelium IgE-FcεRI cross-link induces epithelial barrier disruption in severe T2-high asthma

Chih-Ming Weng; Meng-Jung Lee; Wei Chao; Yuh-Rong Lin; Chun-Ju Chou; Mei-Chuan Chen; Chun-Liang Chou; I-Lin Tsai; Chien-Huang Lin; Kian Fan Chung; Han-Pin Kuo

doi:10.1016/j.mucimm.2023.07.003

Airway epithelium IgE-FcεRI cross-link induces epithelial barrier disruption in severe T2-high asthma

Mucosal Immunol. 2023 Oct;16(5):685-698. doi: 10.1016/j.mucimm.2023.07.003. Epub 2023 Aug 16.

Authors

Affiliations

¹ Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan.
⁴ Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan; Department of Thoracic Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
⁵ Department of Thoracic Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
⁶ Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan; Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁸ Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
⁹ Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan; Department of Thoracic Medicine, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: hpk8828@gmail.com.

PMID: 37536562
DOI: 10.1016/j.mucimm.2023.07.003

Abstract

Although high-affinity immunoglobulin (Ig)E receptor (FcεRI) expression is upregulated in type 2 (T2)-high asthmatic airway epithelium, its functional role in airway epithelial dysfunction has not been elucidated. Here we report the upregulated expression of FcεRI and p-EGFR (Epidermal Growth Factor Receptor), associated with decreased expression of E-cadherin and claudin-18 in bronchial biopsies of severe T2-high asthmatics compared to mild allergic asthmatics and non-T2 asthmatics. Monomeric IgE (mIgE) decreased the expression of junction proteins, E-cadherin, claudin-18, and ZO-1, and increased alarmin messenger RNA and protein expression in cultured primary bronchial epithelial cells from T2-high asthmatics. Epithelial FcεRI ligation with mIgE decreased transepithelial electric resistance in air-liquid interface cultured epithelial cells. FcεRI ligation with mIgE or IgE- Dinitrophenyl or serum of high-level allergen-specific IgE activated EGFR and Akt via activation of Src family kinases, mediating alarmin expression, junctional protein loss, and increased epithelial permeability. Furthermore, tracheal instillation of mIgE in house dust mite-sensitized mice induced airway hyper-responsiveness, junction protein loss, epithelial cell shedding, and increased epithelial permeability. Thus, our results suggest that IgE-FcεRI cross-linking in the airway epithelium is a potential and unnoticed mechanism for impaired barrier function, increased mucosal permeability, and EGFR-mediated alarmin production in T2-high asthma.