title: Poly(inosinic-cytidylic) acid-triggered exacerbation of experimental asthma depends on IL-17A produced by NK cells.
abstract: Viral infection of the respiratory tract represents the major cause of acute asthma exacerbations. dsRNA is produced as an intermediate during replication of respiratory viruses and triggers immune responses via TLR3. This study aimed at clarifying the mechanisms underlying TLR3 triggered exacerbation of experimental allergic asthma. The TLR3 ligand poly(inosinic-cytidylic) acid was applied intranasally to mice with already established experimental allergic asthma. Airway inflammation, cytokine expression, mucus production, and airway reactivity was assessed in wild-type, IL-17A, or IL-23p19-deficient, and in NK cell-depleted mice. Local application of poly(inosinic-cytidylic) acid exacerbated experimental allergic asthma in mice as characterized by enhanced release of proinflammatory cytokines, aggravated airway inflammation, and increased mucus production together with pronounced airway hyperresponsiveness. This was further associated with augmented production of IL-17 by Th17 cells and NK cells. Whereas experimental exacerbation could be induced in IL-23p19-deficient mice lacking mature, proinflammatory Th17 cells, this was not possible in mice lacking IL-17A or in NK cell-depleted animals. These experiments indicate a central role for IL-17 derived from NK cells but not from Th17 cells in the pathogenesis of virus-triggered exacerbation of experimental asthma.
authors.affiliation: Division of Mouse Models of Asthma, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, 23845 Borstel, Germany;
authors.forename: Lars P
authors.initials: LP
authors.lastname: Lunding
authors.affiliation: Division of Experimental Pneumology, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, 23845 Borstel, Germany;
authors.forename: Sina
authors.initials: S
authors.lastname: Webering
authors.affiliation: Division of Experimental Pneumology, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, 23845 Borstel, Germany;
authors.forename: Christina
authors.initials: C
authors.lastname: Vock
authors.affiliation: Fluorescence Cytometry Core Facility, Research Center Borstel, 23845 Borstel, Germany;
authors.forename: Jochen
authors.initials: J
authors.lastname: Behrends
authors.affiliation: Division of Invertebrate Models, Priority Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany;
authors.forename: Christina
authors.initials: C
authors.lastname: Wagner
authors.affiliation: Division of Infection Immunology, Priority Area Infections, Research Center Borstel, 23845 Borstel, Germany; and Member of the German Center for Infection Research, 23845 Borstel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.affiliation: Division of Experimental Pneumology, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, 23845 Borstel, Germany;
authors.forename: Heinz
authors.initials: H
authors.lastname: Fehrenbach
authors.affiliation: Division of Mouse Models of Asthma, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, 23845 Borstel, Germany; mwegmann@fz-borstel.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Wegmann
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D011070:Poly I-C