However, despite notable trends, we did not detect any significant differences in the development of either acute OVA or HDM mediated allergic lung disease in the Nlrp122/2 mice compared to the wild type animals. A number of explanations are possible that may explain our inability to observe significant differences in these lung disease models. The most obvious explanation is that NLRP12 does not have a discernable effect on the pathogenesis of allergic lung disease in the mouse or NLRP12 may function in either a temporal, situational or stimuli specific manner that was not captured in the data generated by the lung inflammation models discussed here. NLRP12 activity may be restricted to a specific cell type or tissue that may contribute to the development of Ibrutinib contact hypersensitivity and atopic dermititis, while not significantly contributing to lung inflammation. This hypothesis is similar to in vivo data published for TLR2, which has been shown to play a vital role in the host immune response during contact hypersensitivity. Similar to NLRP12, TLR2 has been shown to be an essential mediator of the immune response to oxazolone in an allergic contact dermatitis model. However, unlike the findings for OX, Tlr22/2 and wild type mice demonstrated similar levels of inflammation in models involving epicutaneous sensitization with OVA. Other in vivo studies have suggested that TLR2 functions as a negative regulator of allergic airway inflammation following either DMA exposure or acute OVA challenges. In the context of NLRP12, several studies have associated functional studies with gene expression data in humans and rodents. These studies have shown that NLRP12 is differentially expressed between species and transiently increased during various models of lung inflammation. Together, these data support a scenario where NLRP12 does not influence the development of allergic airway inflammation. However, as illustrated by the contact hypersensitivity phenotypes previously reported, it is likely that NLRP12 has a more dramatic role in other models of inflammatory diseases through a temporal and tissue specific mechanism. A second hypothesis for the failure to observe an in vivo phenotype in the lung inflammation models in the Nlrp122/2 mice suggests that the models and analyses we utilized in this study are too broad to effectively discern mild or moderate phenotypes. Indeed, the OVA model described here induced a vigorous Th2 mediated immune response. One valid criticism of this model is that the acute nature and robust inflammation tends to obscure the contribution of several important mediators to the pathogenesis of the disease. To avoid this issue, studies have suggested utilizing chronic models, such as long term OVA exposure or DMA exposure, to assess allergic airway inflammation. Thus, in an effort to address this concern, we also utilized DMA to induce airway inflammation and did not observe any discernable phenotypic differences in the Nlrp122/2 mice. However, we cannot rule out the possibility that higher resolution in vivo models or analysis may reveal a more significant contribution for NLRP12 in mediating subtle aspects of inflammation in the lung. While this study reports that NLRP12 does not affect detectable difference in allergic lung inflammation.