PT  - JOURNAL ARTICLE
AU  - Martijn Nawijn
AU  - Sijranke Post
AU  - Laura Hesse
AU  - Maaike De Vries
AU  - Bart Lambrecht
AU  - Tillie Hackett
AU  - Irene Heijink
TI  - Loss of bronchial epithelial E-cadherin results in spontaneous airway remodeling and eosinophilic inflammation and exaggerated responses to house-dust mite
AID  - 10.1183/13993003.congress-2015.OA1779
DP  - 2015 Sep 01
TA  - European Respiratory Journal
PG  - OA1779
VI  - 46
IP  - suppl 59
4099  - http://erj.ersjournals.com/content/46/suppl_59/OA1779.short
4100  - http://erj.ersjournals.com/content/46/suppl_59/OA1779.full
SO  - Eur Respir J2015 Sep 01; 46
AB  - It is unknown whether impaired barrier function and reduced expression of adherens and tight junction proteins in the airway epithelium of asthmatic patients is cause or consequence of asthma pathogenesis. Here, we test the hypothesis that loss of E-cadherin in airway epithelial cells critically contributes to the pathogenesis of allergic asthma. To this end, we established mice with conditional loss of E-cadherin in the airway epithelium (Cdh1fl/fl Cre+), and compared these to Cre-negative littermates. Naïve mice were examined for lung anatomy and inflammation at several ages, and after House Dust Mite treatment (HDM) in 4 week old mice. Cdh1fl/fl Cre+ mice were viable and displayed no gross abnormalities in lung development. However, pro-inflammatory activation of the airway epithelium was evident from CCL17 and MIP3α production, and inflammatory dendritic cells and eosinophils accumulated in lungs of naïve Cdh1fl/fl Cre+ mice. Cdh1fl/fl Cre+ mice display spontaneous goblet cell metaplasia and hypoplasia of ciliated and secretory airway epithelial cells in the bronchioles. Exposure of 4-week old Cdh1fl/fl Cre+ mice to HDM induced strongly exaggerated eosinophilic airway inflammation compared to Cre- littermates. These data show that airway epithelial loss of E-cadherin induces spontaneous changes characteristic of an asthmatic phenotype, and strongly enhances sensitivity to HDM-induced allergic airway inflammation. Hence, loss of E-cadherin is not merely a consequence of disease, but contributes to asthma pathogenesis, identifying epithelial integrity as a target for novel therapeutic strategies.