Because of the IgG effect, however, we cannot conclude that inhibition of the Th2 response is completely protective in this model, since we do observe a small trend for increased elastance in anti-IL-4 treated mice compared to non-inflamed mice. Nonetheless, it is evident that the exaggerated production of IL-17A and IL-17F is not sufficient to exacerbate AHR above that observed in NO2promoted allergic airway disease. Because STAT6 is required for both the AbMole LOUREIRIN-B development and the effector function of the Th2 response, we subjected STAT6 mice to NO2-promoted allergic sensitization and antigen challenge to determine the role of the Th2 response in this model. In an LPS model of allergic sensitization, STAT6 was required for eosinophils and neutrophils in the airway and AHR following antigen challenge. Similarly, we observed a complete absence of eosinophils and neutrophils in the BAL of STAT6 mice. As expected, we also observed diminution of Th2 cytokines following the restimulation of lung cells in the presence of OVA antigen. In contrast with the LPS sensitizing scheme, STAT6 mice developed comparable AHR to that of WT mice. Differences in experimental protocol may account for this discrepancy. Alternatively, STAT6 can promote a population of Treg cells, and FOXP3+ Treg cells from OVAtolerized mice can undergo cell division upon restimulation in the presence of OVA. Thus, the absence of a Treg population may explain increases in AHR in STAT6 mice despite 
evidence that effector T-cell populations are absent. Others have demonstrated that inhibiting the IL-4R-STAT6 pathway may not be sufficient to inhibit alternative pathways capable of promoting AHR. In a chronic inhalation model, airway inflammation and AHR in STAT6 mice coincided with a switch to a Th1 response. However, we observed minimal IFN�� production in lung restimulation assays. RSV-induced IL-17A was able to elicit mucus metaplasia in the absence of STAT6, and in vitro, IL-17A was sufficient to induce mucus secretion in STAT6, but not in WT, tracheal epithelial cells, AbMole Nitisinone suggesting that STAT6 is a negative regulator of Th17promoted inflammation and that IL-17 may promote mucus production in the absence of a Th2 response. Notably, these results were reported from an adoptive transfer model, which we propose may function differently than an endogenously-generated Th17 response. We observed substantial attenuation of the Th17 response in STAT6 mice and mucin gene expression was comparable to that of noninflamed mice. Similarly, Cxcl5 and Lcn2 expression were decreased, which support the absence of a Th17 response. This finding contradicts the concept that generation of a Th17 response is independent of or negatively-regulated by STAT6. There is evidence for Th2 cells to produce Th17 cytokines. A population of memory Th2 cells in humans and mice was identified that produces IL-17 and coexpresses GATA3 and ROR��t. Whereas adoptive transfer of IL-17+ Th2 cells elicited responses similar to the combined adoptive transfer of Th2 and Th17 cells, synergistically increasing inflammation, we observed no evidence for synergistic interplay of the Th17 and the Th2 response in driving NO2promoted allergic airway inflammation. In our studies, NO2 allergically inflamed and challenged STAT6 mice were essentially absent of airway inflammation, despite the development of AHR. Others have also observed the uncoupling of the immune response with AHR. In these studies, we observed that gene expression of defensins, A20, Nox4, S100a9, Brp-39, Chia did not correlate with AHR development following NO2promoted allergic airway disease.