IL‐17 regulates dendritic cell migration to the peribronchial lymph nodes and allergen presentation in experimental allergic asthma

IL-17 is associated with different phenotypes of asthma, however, it is not fully elucidated how it influences induction and maintenance of asthma and allergy. In order to determine the role of IL-17 in development of allergic asthma, we used IL-17A/F double knockout (IL-17A/F KO) and wild type (wt) mice with or without neutralization of IL-17 in an experimental allergic asthma model and analysed airway hyperresponsiveness, lung inflammation, T helper cell polarization and dendritic cells (DC) influx and activation. We report that absence of IL-17 reduced influx of DCs into lungs and lung draining lymph nodes. Compared to wt mice, IL-17A/F KO mice or wt mice after neutralization of IL-17A showed reduced airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and immunoglobulin E levels. DCs from draining lymph nodes of allergen-challenged IL-17A/F KO mice showed reduction in expression of migratory and costimulatory molecules CCR7, CCR2, MHC-II, and CD40 compared to wt DCs. Moreover, in vivo stimulation of adoptively transferred antigen-specific cells was attenuated in lung-draining lymph nodes in absence of IL-17. Thus, we report that IL-17 enhances airway DC activation, migration and function. Consequently, lack of IL-17 leads to reduced antigen-specific T cell priming and impaired development of experimental allergic asthma. This article is protected by copyright. All rights reserved.