ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1606915
Innate epithelial and functional differences in airway epithelium in children with acute wheeze
Provisionally accepted
Kevin Looi1,2,3*
Thomas Iosifidis1,2,3,4
Saraya Harrison3,5
Stephen Michael Stick6
Peter Le Souef1,3,6Ingrid Laing1,3Anthony Kicic1,2,3,4- 1Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, Australia
- 2School of Population Health, Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, Australia
- 3Centre for Child Health Research, Telethon Kids Institute, University of Western Australia, Crawley, Western Australia, Australia
- 4Centre for Cell Therapy and Regenerative Medicine, School of Medicine, University of Western Australia, Perth, Western Australia, Australia
- 5School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia
- 6Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Western Australia, Australia
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Early childhood wheeze is a major risk factor for asthma. However, not all children who wheeze will develop the disease. The airway epithelium has been shown to be involved in asthma pathogenesis. Despite this, the airway epithelium of children with acute wheeze remains poorly characterized.Methods: Upper airway epithelial cells (AEC) from children with acute wheeze and non-wheeze controls were cultured and expanded. Markers of epithelial lineage (Cytokeratin (KRT)-5, -19) and vimentin were assessed via qPCR and immunocytochemistry. Inflammatory cytokines (Interleukin (IL)-1β, -6, and -8) were measured using ELISA. Tight junction (TJ) protein expression and barrier integrity were determined via In-Cell Western and paracellular permeability assays, respectively.Results: Upper AECs from children with acute wheeze had significantly higher KRT19 and lower vimentin gene expression compared to non-wheeze controls but similar KRT5 levels. Similar staining intensities of KRT5 and KRT19 proteins were observed in both cohorts. IL-6 and IL-8 levels were not significantly different, but IL-1β was increased in cultures from children with acute wheeze compared to controls. Tight junction protein expression of claudin-1, occludin and ZO-1 were significantly lower in acute wheeze cohorts, concomitant with increased paracellular permeability.Airway epithelium of children experiencing acute wheeze appears abnormal, primarily with compromised epithelial barrier integrity.
Keywords: Asthma, viral-induced wheeze, Airway epithelium, Conditional Reprogramming, cell culture
Received: 06 Apr 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Looi, Iosifidis, Harrison, Stick, Le Souef, Laing and Kicic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kevin Looi, Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, Australia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.