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Prime role of IL-17A in neutrophilia and airway smooth muscle contraction in a house dust mite–induced allergic asthma model

Published:January 30, 2015DOI:https://doi.org/10.1016/j.jaci.2014.12.1872
      Asthma is a bronchial inflammatory disease leading to airway hyperresponsiveness (AHR) and reversible airflow obstruction. The incidence of asthma has increased considerably over the past 50 years, with approximately 300 million people affected worldwide.
      • Fanta C.H.
      Asthma.
      Most of the animal studies have demonstrated that CD4 TH2 cells are central in the orchestration and amplification of allergic asthma. However, negative results obtained from TH2-focused human clinical trials have highlighted the importance of considering the large variety of asthma phenotypes.
      • De Boever E.H.
      • Ashman C.
      • Cahn A.P.
      • Locantore N.W.
      • Overend P.
      • Pouliquen I.J.
      • et al.
      Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial.
      Indeed, human asthma is highly heterogeneous and is not always only due to TH2-driven airway inflammation.
      • Wenzel S.E.
      Asthma phenotypes: the evolution from clinical to molecular approaches.
      • Woodruff P.G.
      • Modrek B.
      • Choy D.F.
      • Jia G.
      • Abbas A.R.
      • Ellwanger A.
      • et al.
      T-helper type 2-driven inflammation defines major subphenotypes of asthma.
      Recently, many studies have suggested that IL-17A, a cytokine mainly produced by TH17 cells, is involved in certain severe cases of asthma by regulating neutrophilic inflammation and steroid resistance.
      • Chesné J.
      • Braza F.
      • Mahay G.
      • Brouard S.
      • Aronica M.
      • Magnan A.
      IL-17 in severe asthma: where do we stand?.
      However, support for this theory remains modest because certain reports have demonstrated (1) that IL-17A or TH17 cells alone are not sufficient to trigger the disease and (2) that, intriguingly, IL-17A can mediate anti-inflammatory mechanisms. Consequently, we aimed to determine the contribution of IL-17A in a mouse model of acute asthma induced by house dust mites (HDMs).
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