The role of IL-17 producing NK cells and other innate immune cells in poly(I:C) triggered exacerbation of experimental asthma

Autor: Jochen Behrends, Heinz Fehrenbach, Christina Vock, Lars Lunding, Michael Wegmann, Sina Webering, Christoph Hölscher
Rok vydání: 2016
Předmět:
Zdroj: 5.3 Allergy and Immunology.
DOI: 10.1183/13993003.congress-2016.pa1102
Popis: Background: Viral infection of the respiratory tract represents the major cause of acute asthma exacerbations. Viral dsRNA triggers immune responses via Toll-like receptor 3. Poly(I:C) alone is sufficient to trigger an exacerbation of experimental asthma in mice. Objective: This study aimed at investigating the underlying mechanisms of experimental asthma exacerbation and identifying the involved immune cells. Methods: Poly(I:C) was applied intranasally to mice with already established experimental allergic asthma. Airway inflammation, cytokine expression, mucus production, and airway reactivity was assessed in WT, IL-17A, IL-23p19, or RORγt-deficient, and in NK cell-depleted mice. FACS staining for CD4 + , CD8 + , NK cells, NKT cells, iNKT, cells, ILCs, and MAIT cells were performed, respectively. Results: Poly(I:C)-induced exacerbation of experimental asthma in mice is characterized by aggravation of airway inflammation, proinflammatory cytokine release, mucus production and airway hyperresponsiveness. Strikingly, this was further associated with increased levels of IL-17 and infiltration of Th17 cells and IL-17 + NK cells. Exacerbation could be evoked in WT mice as well as in animals deficient either for IL-23p19 or RORγt. In contrast, it was not possible to trigger an exacerbation in IL-17A deficient or NK cell-depleted mice. Conclusions: These experiments indicate a central role for IL-17 derived from NK cells but not from Th17 cells in experimental asthma exacerbation. These IL-17-producing NK cells cannot be attributed as typical NK1/17 cells and may represent a new distinct NK subpopulation and a new target for the therapy of asthma exacerbations.
Databáze: OpenAIRE