IL-4 and IL-17 Are Required for House Dust Mite-Driven Airway Hyperresponsiveness in Autoimmune Diabetes-Prone Non-Obese Diabetic Mice.

Anne-Perrine Foray,François Machavoine,Lucienne Chatenoud,Maria Leite-De-Moraes,Céline Dietrich,Coralie Pecquet

doi:10.3389/fimmu.2020.595003

Abstract

Allergic asthma is characterized by airway inflammation with a Th2-type cytokine profile, hyper-IgE production, mucus hypersecretion, and airway hyperreactivity (AHR). It is increasingly recognized that asthma is a heterogeneous disease implicating complex immune mechanisms resulting in distinct endotypes observed in patients. In this study, we showed that non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, undergo more severe allergic asthma airway inflammation and AHR than pro-Th2 BALB/c mice upon house dust mite (HDM) sensitization and challenge. The use of IL-4-deficient NOD mice and the in vivo neutralization of IL-17 demonstrated that both IL-4 and IL-17 are responsible by the exacerbated airway inflammation and AHR observed in NOD mice. Overall, our findings indicate that autoimmune diabetes-prone NOD mice might become useful as a new HDM-induced asthma model to elucidate allergic dysimmune mechanisms involving Th2 and Th17 responses that could better mimic some asthmatic endoytpes.

Highlights

Asthma is an heterogenous immune pathology characterized by wheeze, cough, shortness of breath, chest tightness, and variable degrees of airflow limitation
Neutrophils, or lymphocytes were observed in bronchoalveolar lavage fluid (BALF) from BALB/c or non-obese diabetic (NOD) control mice treated with saline solution
Bearing in mind that IL-17 is involved in certain severe cases of asthma likely by regulating neutrophilic inflammation [10] together with our present observation that Vg1+ gd and CD4+ T cells from the lung of NOD house dust mite (HDM) mice produced high levels of this cytokine (Figure 2), and that NOD IL-4KO HDM mice presented higher levels of neutrophils in the airway (Figures 3A, B), we further examined whether IL-17 contributed to the airway inflammation and airway hyperreactivity (AHR) observed in NOD IL-4KO HDM mice

Summary

Introduction

Asthma is an heterogenous immune pathology characterized by wheeze, cough, shortness of breath, chest tightness, and variable degrees of airflow limitation. These symptoms are associated with different patterns of inflammation [1,2,3,4,5]. Asthma is distinguished in two types: allergic and non-allergic. Inflammation is primarily caused by type 2 immune responses mediated through the Th2 cytokines IL-4, IL-5, and IL-13 and associated with increased Th2 cells and eosinophils in the airways [6, 7]. Non-allergic asthma is mainly triggered by an inflammatory response to viral infections with a major neutrophilic component [7]. There is Abbreviations: AHR, airway hyperreactivity; BALF, bronchoalveolar lavage fluid; HDM, house dust mite; ILT, innate-like T cells; iNKT, invariant natural killer T cells; NOD, non-obese diabetic

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Discussion

Conclusion