Comparison of Airway Remodeling in Two Different Endotypes of Allergic Asthma

Abstract

Different endotypes of asthma were described in human. Atopic asthma is a T-helper 2 (Th2)-mediated disease consisting mainly of an eosinophilic inflammation in the airways. Other endotypes show neutrophilic inflammation of the airways that is probably based on a Th17 response. There are several mouse models described in the literature to study the Th2 polarized eosinophilic disease, however, only a few models are available which characterize the neutrophilic endotype. The aim of this study was to compare both endotypes in relation to the severity of the allergen-induced inflammation. Groups of either Balb/c or DO11.10 mice were sensitized with ovalbumin (OVA) adsorbed to aluminum hydroxide. Mice were subsequently challenged with OVA for different periods of time. They were evaluated for airway hyperreactivity (AHR), cytokine production, airway inflammation, and remodeling of the airways. As expected, Balb/c mice developed a Th2 response with AHR, eosinophilic airway inflammation, and allergen-specific IgE and IgG1. By contrast DO11.10 mice showed a mixed Th1/Th17 response with strong neutrophilic airway inflammation, IgG2a, but only limited induction of AHR. While Balb/c mice showed remodeling of the airways with subepithelial fibrosis and goblet cell metaplasia, airway remodeling in DO11.10 mice was marginal. Both airway inflammation and remodeling resolved after prolonged periods of challenge in both models. In conclusion, strong allergen-induced airway remodeling in mice seems to be triggered by the specific conditions arising from infiltration with eosinophilic granulocytes in the lung. A Th1/Th17 response leading to neutrophilic inflammation does not seem to be sufficient to induce pronounced airway remodeling.