Pneumologie 2015; 69 - A29
DOI: 10.1055/s-0035-1556621

Pulmonary IL-13 expression is increased by airway surface dehydration in vivo

S Christochowitz 1, C van Bodegom 1, S Schmidt 1, E Maier 1, M Hagner 1, J Fellenberg 2, MA Mall 1, B Fritzsching 1
  • 1Department of Translational Pulmonology, Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Germany
  • 2Department of Orthopedics and Traumatology, University Hospital Heidelberg, Germany

Introduction: We have previously demonstrated that mice with airway specific overexpression of the epithelial Na+ channel (βENaC-Tg) exhibit airway surface dehydration and eosinophilic airway inflammation in juvenile mice (Mall MA, Am J Respir Crit Care Med 2008). We hypothesized that airway surface dehydration may increase the susceptibility for allergic airway inflammation and treatment with allergen could induce IL-13 expression in vivo. Here, we evaluated cellular sources of IL-13 expression in response to allergen treatment in wild-type and βENaC-Tg mice.

Methods: Juvenile wild-type and βENaC-Tg mice were challenged intratracheally for one week with Aspergillus fumigatus (Af) extract. In vitro restimulated whole lung-derived leukocytes were analyzed for IL-13 expression by multicolor flow cytometry. Laser microdissection (LMD) of the airway epithelium and subsequent nested qPCR were performed for quantification of airway-specific mRNA expression of IL-13, IL-33, IL-25, TSLP and periostin. IL-13 expression was confirmed by immunohistochemistry with IL13-/- mice-derived lung tissue as negative control.

Results: Intrapulmonary exposure of Af significantly increased airway eosinophils and pulmonary IL-13 in βENaC-Tg mice. We observed elevated numbers of pulmonary IL-13+-cells among macrophages, Th2-, B- and ILC2-cells in βENaC-Tg mice by 11-color flow cytometry, which was further increased in response to Af treatment in Th2- and ILC2-cell populations. LMD revealed airway epithelial cell-specific expression of IL-13 and IL-33 but not TSLP and IL-25 in βENaC-Tg mice. Immunostaining confirmed epithelium-mediated IL-13 protein expression, which was enhanced after Af challenge in βENaC-Tg mice.

Conclusion: We demonstrate that airway surface dehydration is a risk factor for allergic airway inflammation including increased frequencies of IL-13+-cells in response to allergen. Furthermore, expression of IL-13 is not limited to Th2 cells, but also ILC2 cells and airway epithelium provide substantial amounts of IL-13 in vivo.

*Presenting author