Critical role of IL-17R signaling in granulocyte recruitment and airway hyperreactivity in an Aspergillus model of asthma (96.7)

Abstract Rationale IL-17 is a proinflammatory cytokine that enhances neutrophil recruitment in response to allergen in murine lung. In an Aspergillus fumigatus (Af)-induced asthma model, wild-type C57BL/6 mice develop bronchial inflammation and hyperreactivity. We hypothesized that, compared to C57BL/6, Af sensitized IL-17R KO mice would have reduced neutrophil recruitment to the lung, airway resistance and hyperreactivity. Methods C57BL/6 and IL-17R KO male mice, 6–8 wk old, were sensitized intraperitoneally with 40 ug Af extract and 2 mg Al(OH)3 on days 0 and 7, and intratracheally with 25 ug Af on days 21, 22, and 23. Bronchoalveolar lavage (BAL) differential cell counts and cytokine analysis were done at 24 and 72 hr. Flexivent was performed at 24 hr to assess airway physiology. Results WT mice had significant influx of both neutrophils and eosinophils in response to Af at 24 hr. In contrast, IL-17R KO mice showed reduced neutrophil and eosinophil emigration to the lung which was associated with lower KC and eotaxin levels in BAL fluid. Furthermore, Flexivent data showed lower airway resistance and bronchial hyperreactivity in IL-17R KO mice. Conclusion Our findings in Af treated IL-17R KO mice of decreased pulmonary neutrophil and eosinophil recruitment at 24 hr suggest that IL-17 promotes granulocyte recruitment as well as airway hyperreactivity. Funding: NHLBI