Poly(inosinic-cytidylic) Acid–Triggered Exacerbation of Experimental Asthma Depends on IL-17A Produced by NK Cells
| Autor: | Jochen Behrends, Christina Vock, Christoph Hölscher, Heinz Fehrenbach, Sina Webering, Lars Lunding, Christina Wagner, Michael Wegmann |
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| Rok vydání: | 2015 |
| Předmět: |
Exacerbation
Immunology Interleukin-23 Proinflammatory cytokine Pathogenesis Mice Immune system medicine Animals Immunology and Allergy Respiratory system Asthma Mice Knockout business.industry Interleukin-17 medicine.disease Killer Cells Natural Disease Models Animal Poly I-C medicine.anatomical_structure TLR3 Disease Progression Cytokines Th17 Cells Female Chemokines business Respiratory tract |
| Zdroj: | The Journal of Immunology. 194:5615-5625 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1402529 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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