@article {Lunding1720, author = {Lars Lunding and Sina Webering and Christina Vock and Christoph H{\"o}lscher and Jochen Behrends and Heinz Fehrenbach and Michael Wegmann}, title = {TLR-3 triggered exacerbation of experimental asthma depends on IL-17 producing NK cells}, volume = {44}, number = {Suppl 58}, elocation-id = {1720}, year = {2014}, publisher = {European Respiratory Society}, abstract = {Exacerbations are a common event in asthma patients and may result in severe symptoms. Typically, the inflammatory phenotype of acute asthma exacerbations is characterized by increased numbers of eosinophils together with large infiltration of neutrophils. Clinical studies revealed viral infections of the airways as the main trigger. Double stranded RNA is produced as an intermediate during replication of all major respiratory viruses that can be sensed via toll-like receptor 3 (TLR3). Therefore, we propose a key role for TLR3 in the pathogenesis of acute asthma exacerbations. Our study aimed at i) establishing a mouse model of TLR3 trigged asthma exacerbation, ii) clarifying the underlying mechanisms, and iii) identifying the cell type(s) directing the inflammatory response in acute exacerbation.Intranasal application of synthetic TLR3 ligand poly(I:C) induced an exacerbation of experimental allergic asthma characterized by pronounced airway hyperresponsiveness (AHR), marked infiltration of neutrophils, mucus production, enhanced release of pro-inflammatory cytokines and increased numbers of TH17 and IL-17 producing NK cells. All these characteristics were absent in IL-17A deficient mice, indicating an essential role of IL-17A in TLR3 triggered asthma exacerbation. In IL-23p19 deficient mice, which lack TH17 cells, local application of poly(I:C) again triggered asthma exacerbation. Interestingly, in mice with antibody depleted NK cells AHR, mucus production and number of eosinophils where ameliorated. Therefore, IL-17 producing NK cells and not TH17 cells play a major role in TLR3 triggered exacerbation of allergic asthma in mice.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/44/Suppl_58/1720}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }