DeStefano, Stephanie and Grychtol, Ruth and Funken, Dominik and Habener, Anika and Tamm, Stephanie and Stanke, Frauke and Greiner, Wolfgang and Beyer, Kirsten and Hamelmann, Eckard and Kabesch, Michael and von Mutius, Erika and Schaub, Bianca and Jirmo, Adan Chari and Hansen, Gesine (2025) NLRP3 regulates epithelial barrier integrity and protects from airway hyperresponsiveness in experimental allergic asthma. FRONTIERS IN IMMUNOLOGY, 16: 1655205. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Background The inflammasome NLRP3 (NOD-like receptor family pyrin domain containing 3) is critical for epithelial barrier integrity. Allergic asthma is characterized by airway inflammation, airway hyperresponsiveness (AHR), and mucus hypersecretion. To date, the key players and underlying mechanisms in the interaction between NLRP3 and epithelial barrier integrity in type 2-mediated allergic asthma are poorly understood.Objective Our study aims to evaluate the protective mechanisms of NLRP3 on airway epithelium and its structural and functional components during type 2-mediated allergic asthma inflammation.Methods Using an experimental model of allergic airway disease, NLRP3-deficient (NLRP3-/-) and wild-type (WT) mice were analyzed for AHR, mucus hyperplasia, airway inflammation and the alterations in the airway epithelium transcriptome.Results In comparison to WT mice, NLRP3-/- mice exhibited significantly enhanced AHR and mucus production, while eosinophilic airway inflammation was comparable. Analysis of epithelial cell markers revealed decreased gene expression of the tight junction proteins Cld-18 and Tjp-1, and decreased expression of the epithelial transmembrane protein E-cadherin in the lungs of na & iuml;ve NLRP3-/- mice compared to WT mice. Moreover, intranasal treatment with FITC-labelled OVA resulted in significantly higher allergen uptake by lung conventional dendritic cells (cDCs) in NLRP3-/- compared to WT mice indicating increased epithelial leakiness. In vitro, inhibition of NLRP3 in the human bronchial epithelial cell line 16HBE14o- with MCC950 resulted in the downregulation of Tjp-1 and CDH1 (E-cadherin).Conclusion NLRP3 is essential for epithelial barrier integrity in the lung and protects from the development of allergic asthma in a murine model.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TIGHT JUNCTIONS; E-CADHERIN; INFLAMMASOME; ACTIVATION; CELLS; RESPONSES; DYSFUNCTION; EXPRESSION; NLRP3; Th2-inflammation; asthma; epithelial barrier; tight junction proteins |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 May 2026 06:10 |
| Last Modified: | 19 May 2026 06:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67465 |
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