Many epidemiological and clinical evidences suggest that obesity is an important risk factor for asthma, but the underlying mechanisms remain poorly understood. Besides adaptive immunity and adipokines, innate mechanisms have been involved in both diseases. Given the recent implication of group 2 innate lymphoid cells (ILC2) in asthma and adipose tissue homeostasis, and of ILC3 in obesity-associated airway hyperresponsiveness (AHR), the purpose of this study was to characterize the contribution of adaptive T helper cells versus ILC in a model of house dust mite (HDM)-induced asthma exacerbation by diet-induced obesity.

Obesity was induced by a 60% high fat diet (HFD), and lean mice were fed with a low fat diet (LFD). Twelve weeks later, asthma was induced by intranasal administration of HDM. The cardinal features of experimental asthma were evaluated in combination with a flow cytometric analysis of the different adaptive or innate lymphoid population proportions and cytokine production.

In lean mice, HDM induced the classical parameters of allergic asthma including increased airway hyperresponsiveness, IgE production, cell recruitment in the bronchoalveolar lavage with eosinophil, lymphocyte and neutrophil infiltrations. Histologic staining confirmed increased mucus accumulation in lungs of asthmatic mice. Feeding mice with HFD resulted in the exacerbation of some features of asthma including serum concentrations of IgE, recruitment of eosinophils in the bronchoalveolar lavage and airway hyperreactivity. Evaluation of the T cell cytokine profile in the lung protein extracts showed an exacerbation of the Th2 and Th17 profiles in obese mice compared to lean mice after HDM challenge. Moreover, the number of ILC2 and ILC3 NCR⁻ cells was increased in HDM-challenged obese mice compared to HDM-challenged lean mice, with an increased intracellular expression of IL-13, IL-17A and IL-22. At the mRNA level, IL-33 mRNA was strongly increased in HDM-challenged obese mice as compared with HDM-challenged lean mice, suggesting that IL-33 might contribute to the induction of ILC2 in obese asthmatic mice. These results support the concept that obesity may exacerbate allergen-induced asthma by a mechanism involving in part ILC2 and ILC3.