Airway surface dehydration is a novel risk factor for allergic airway inflammation B. Fritzsching, L. Dai, C. Van Bodegom, J. Schatterny, S. Hirtz, Z. Zhou-Suckow, M. Hagner, S. Christochowitz, M. A. Mall (Heidelberg, Germany)
Source: International Congress 2014 – Novel approaches in transcriptomics and epigenomics in inflammatory lung diseases and lung cancer
Disease area: Airway diseasesAbstract Introduction: Our recent evidence from mice lacking the epithelial Cl- channel SLC26A9 and mice with airway specific overexpression of the amiloride-sensitive epithelial Na+ channel (b ENaC-Tg) suggests that dysregulated epithelial ion transport and airway surface dehydration may be implicated in the pathogenesis of allergic airway disease (Anagnostopoulou et al., JCI 2012 and Mall et al., AmJRespirCritCare Med 2008). We hypothesized that airway surface dehydration and reduced mucociliary clearance may increase the susceptibility for allergic airway inflammation due to reduced allergen clearance.Methods: Aspergillus fumigatus extract (Af) was applied by repeated intratracheal instillations into b ENaC-Tg mice (C57BL/6) and BAL cell counts, airway morphology, airway hyperresponsiveness (AHR, by Flexivent lung function) and allergen clearance were compared to wild-type mice. IL-13 expressing cell types in the lung were identified by 11-color flow cytometry.Results: Airway eosinophils, pulmonary IL-13 expression and AHR were significantly increased in Af-challenged compared to vehicle-treated b ENaC-Tg mice. 11-color flow cytometry of lung tissue detected IL-13 secretion from Th2 cells, but also from ILC-2 and airway epithelial cells. IL-13 effector functions were further highlighted by STAT6 deletion, a critical molecule for IL-13 signaling. These bENaC-Tg/STAT6-/- mice were protected from Af-induced airway eosinophilia, mucus obstruction and elevated IL-13 expression.Conclusion: Collectively, our results indicate that airway surface dehydration and impaired mucus and allergen clearance constitute risk factors for key pathologies in allergic airway disease.Acknowledgements: DFG (DFG MA 2081/3-2).Rating:
You must login to grade this presentation.
Share or cite this content
Citations should be made in the following way:
B. Fritzsching, L. Dai, C. Van Bodegom, J. Schatterny, S. Hirtz, Z. Zhou-Suckow, M. Hagner, S. Christochowitz, M. A. Mall (Heidelberg, Germany). Airway surface dehydration is a novel risk factor for allergic airway inflammation. Eur Respir J 2014; 44: Suppl. 58, 397
You must login to share this Presentation/Article on Twitter, Facebook, LinkedIn or by email.
Member's Comments
Related content which might interest you:
Related content which might interest you: