PT  - JOURNAL ARTICLE
AU  - Benedikt Fritzsching
AU  - Lu Dai
AU  - Charlotte van Bodegom
AU  - Jolanthe Schatterny
AU  - Stephanie Hirtz
AU  - Zhe Zhou
AU  - Marcus Mall
TI  - Airway surface dehydration confers susceptibility to allergic airway inflammation in vivo
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - P4741
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/P4741.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/P4741.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - Introduction: Recent evidence from mice lacking the epithelial Cl- channel SLC26A9 and mice with airway specific overexpression of the amiloride-sensitive epithelial Na+ channel (βENaC-Tg) suggests that airway surface dehydration is implicated in the pathogenesis of allergic airway disease (Anagnostopoulou et al., J Clin Invest 2012 and Mall et al., Am J Respir Crit Care 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.Results: We demonstrate that airway surface dehydration in βENaC-Tg mice results into airway hyperresponsiveness as determined by lung function with the Flexivent system. Furthermore, intrapulmonary exposure to Aspergillus fumigatus extract significantly increased airway eosinophils and pulmonary IL-13 in βENaC-Tg mice. 11-color flow cytometry of BAL and lung tissue detected IL-13 secretion from Th2 cells, but also from other cells including recently discovered Lung Natural Helper cells and airway epithelium cells. IL-13 effector functions were further highlighted by introducing a genetic deletion of STAT6, a critical molecule for IL-13 signaling, to βENaC-Tg mice. These βENaC-Tg STAT6-/- mice were protected from airway eosinophilia, airway mucus obstruction and elevated IL-13 expression.Conclusion: Collectively, our results indicate that airway surface dehydration and impaired mucus clearance constitutes a risk factor for key pathologies in allergic airway disease including increased IL-13 production, eosinophilic inflammation and airway hyperresponsiveness.Acknowledgements: DFG (DFG MA 2081/3-2), BMBF (DZL 82DZL00401).