Epidermal growth factor receptor in airway remodelling during allergic airway disease – divergent roles during early life and adulthood?

Abstract

Lung function deficits established in asthmatic children persist into adulthood, but the mechanisms are not well understood. Airway remodelling is a key pathological feature of paediatric and adult asthma and may contribute to loss of lung function. Epidermal growth factor receptor (EGFR) was shown to be overexpressed in paediatric and adult asthmatics. In addition, several in vivo studies using rodent models of allergic airway disease (AAD) have described a role for EGFR signalling in driving impaired lung function and airway remodelling in adult animals. Here, we aimed to study the role of EGFR in early life AAD. We used flow-sorted murine lung cell populations to investigate EGFR expression at different stages of postnatal development. qPCR analysis revealed high expression of EGFR and ligands primarily in epithelial and structural cells in both neonatal and adult mice and high expression of EGFR on epithelial cells was confirmed by flow cytometry. To assess the role of EGFR during neonatal AAD, an EGFR inhibitor was administered during the last three of five weeks of inhaled allergen exposure. Our findings indicate that EGFR inhibition in neonatal mice resulted in worsened lung function, as measured by a 2-fold increase in airway resistance (area under the curve), whereas lung function in adult mice was unaffected by EGFR inhibition. Interestingly, we did not observe any changes in pulmonary inflammation, allergic sensitisation, mucus production or remodelling-associated gene expression upon EGFR inhibition in either model. These results indicate that EGFR is present in lungs at all stages of life and that, in contrast to its widely described pathogenic contribution to airway remodelling of adult animals, signalling through EGFR may play a protective role during early life AAD.