Innate epithelial and functional differences in airway epithelium of children with acute wheeze

Kevin Looi1,2,3, Thomas Iosifidis1,2,3,4, Saraya Harrison3,5

  • 1Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, Australia.

Insights

Children with acute wheeze show abnormal airway epithelium, specifically compromised barrier integrity. This finding is crucial for understanding asthma development in early childhood.

Area of Science:

  • Respiratory Medicine
  • Pediatric Pulmonology
  • Epithelial Biology

Background:

  • Early childhood wheeze is a significant risk factor for developing asthma.
  • The airway epithelium plays a role in asthma pathogenesis.
  • The specific characteristics of airway epithelium in children with acute wheeze are not well understood.

Purpose of the Study:

  • To investigate the characteristics of upper airway epithelial cells (AECs) in children with acute wheeze.
  • To compare AECs from wheezing children with those from non-wheezing controls.
  • To assess epithelial cell markers, inflammatory cytokine profiles, and barrier function.

Main Methods:

  • Cultured and expanded upper AECs from children with acute wheeze and controls.
  • Assessed epithelial lineage markers (Cytokeratin 5 and 19, vimentin) using qPCR and immunocytochemistry.
  • Measured inflammatory cytokines (IL-1β, IL-6, IL-8) and evaluated tight junction protein expression and barrier integrity.

Main Results:

  • Children with acute wheeze exhibited altered gene expression of KRT19 and vimentin, with elevated IL-1β.
  • No significant differences were found in KRT5 protein levels or IL-6 and IL-8.
  • Significantly reduced expression of tight junction proteins (claudin-1, occludin, ZO-1) and increased paracellular permeability were observed in the acute wheeze group.

Conclusions:

  • The airway epithelium in children experiencing acute wheeze is characterized by abnormalities.
  • Compromised epithelial barrier integrity is a key feature in children with acute wheeze.
  • These findings highlight potential mechanisms linking early wheeze to asthma development.
Abstract

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