Th17-mediated allergic airway disease acts through IL-17A/IL-17R signaling to recruit neutrophils, and both IL-17A and neutrophils are required to promote AHR development. Therefore, we sought to address specifically whether IL-17A was required for AHR in our model of NO2promoted allergic airway disease. Similar to our previous reports, we clearly observed mixed Th2/Th17 airway inflammation, including the recruitment of neutrophils and eosinophils, in NO2-promoted allergic airway disease. Neutrophil recruitment required IL-17A, likely through the induction of Cxcl5 by pulmonary epithelial cells, validating that IL-17A is a critical contributor to airway neutrophila in NO2-promoted allergic airway disease. However, contrary to our hypothesis, treatment with an IL-17Aneutralizing antibody did not impact the AbMole Oxytocin Syntocinon development of MCh hyperresponsiveness compared to untreated NO2-sensitized and challenged mice and resulted in increased elastance compared to mice administered and isotype control antibody. We have previously noted a trend for decreased neutrophils in IL-1R mice, and in these studies, we observed a significant diminution of neutrophils in NO2-promoted allergic airway disease following antigen challenge. Yet surprisingly, IL-1R mice developed exacerbated AHR compared with WT mice. Neutrophil activity is thought to mediate asthma by inducing structural damage via the release of enzymes from granules. In a model of alum/OVA allergic airway disease, inhibition of neutrophil elastase prevented AHR, mucus production, eosinophil recruitment to the airway, and Th2 cytokine production, as well as eotaxin in the BAL, supporting a role for neutrophil elastase in the generation of Th2 responses as well. In contrast, a study conducted in an alum/OVA model demonstrated that the inhibition of neutrophils by blocking IL-1R signaling early during antigen challenge did not impact the development of AHR. We also observed that inhibition of neutrophil recruitment with either anti-IL-17A neutralizing antibody, or through genetic deficiency in IL-1R, provided no protection against AHR in our asthma model. Thus, our results do not support a role for IL-17A or neutrophil recruitment in the development of AHR in NO2-promoted allergic sensitization. We have not detected elastase activity at the time of analysis in either BAL cells or BAL fluid, although incubating BAL cells for 24h at RT resulted in elastase activity, suggesting that the neutrophils recruited to the lavageable airspaces in our model at the time of analysis are inactive. AbMole Indinavir sulfate Furthermore, we have conducted antibody-mediated neutrophil depletion at the time of antigen challenge in our model and found substantial variability in its effect on AHR. The involvement of the IL-1R in promoting Th17 responses that then regulate AHR development have not to our knowledge been published. Toluene diisocyanate-mediated AHR and mucus production required IL-1R signaling, but IL-17 was not measured in this model. In HDM-promoted allergic airway disease and an alum-independent model involving intraperitoneal OVA injection, IL-1R was required for the development of a Th2 response. In NO2-promoted allergic airway disease, the IL-1R is critical for the Th17 response but not the Th2 response. Whereas the IL-1Rdependent Th17 response has been implicated in experimental allergic encephalomyelitis susceptibility, its importance has also been a subject of debate since IL-17A overexpressing mice were equally susceptible to develop EAE and had similar disease severity, whereas minimal protection was elicited by anti-IL-17A treatment of IL-17F mice.