T mice. The number of Alcian blue-stained goblet cells significantly increased in mev mice compared with WT mice. Deletion of the IL-4 and IFN-c genes significantly decreased goblet cells in the nasal airways of mev mice. However, deletion of IL-13 gene had little effect on goblet cells. Discussion In this study we showed evidence to support the importance of SHP-1 in the maintenance of immunologic homeostasis in the nasal airways. If the function of the SHP-1 enzyme, one of the important inhibitors of IL-4Ra signaling pathway, is decreased or lost, robust eosinophilic inflammation develops in the nasal mucosa, in the absence of any extra stimulation. This suggests that under normal conditions, SHP-1 is critical in maintaining a threshold for cell and tissue responses to normal environmental stimulation. Nasal cytology and histology also demonstrated a spontaneous eosinophilic inflammation in the mev mice. The Spontaneous Rhinitis in SHP-1 Deficient Mice 4 Spontaneous Rhinitis in SHP-1 Deficient Mice mRNA expression of Th2 cytokines is up-regulated and is accompanied by a decrease in IFN-c. In addition, eotaxin in the NAL fluids significantly increased in the mev mice compared with WT mice. Therefore, SHP-1 deficiency-mediated nasal inflammation is 
Th2-skewed. Recently, our group reported asthma-like lung inflammation and rhinitis-like nasal inflammation in the mev mice. Therefore, under normal conditions, SHP-1 is an important immune regulator in both upper and lower airways. The SHP-1 deficient mev mice as a Th2-dominated rhinitis model can be utilized to unravel the underlying immune mechanisms of allergic rhinitis and chronic rhinosinusitis with nasal polyposis. 5 Spontaneous Rhinitis in SHP-1 Deficient Mice Allergic airway inflammation, such as seen in asthma and allergic rhinitis, is thought to be mainly orchestrated by Th2 immunity. The Th2/Th1 paradigm is a traditional concept that can explain some of the mechanisms underlying the immune homeostasis or pathologic inflammatory conditions such as asthma and autoimmune diseases. Different from IL-4 and IL-5, IL13 and IFN-c are constitutively expressed in the nasal mucosa of unchallenged WT mice, suggesting that under normal conditions, IL-13 and IFN-c may be present to maintain the balance of Th2/ Th1 paradigm in the upper airway. This is also in contrast to the lower airways, where no IL-13 or IFN-c can be found under normal conditions. It is well recognized that allergic LGX818 web diseases are closely associated with an enhanced Th2 immune response with high levels of IL-4, IL-5, and IL-13, but accumulating evidence also implicates downregulated Th1 immune responses in the pathogenesis of allergy 6 Spontaneous Rhinitis in SHP-1 Deficient Mice . Th1 lymphocytes and cytokines such as IFN-c and IL-12 may counteract or suppress Th2 responses in allergic diseases. Defective IFN-c production predisposes toward the development of allergic diseases. For example, patients with severe asthma present significantly reduced IFN-c production in response to allergen when compared to controls. In our study, with regard to the Th1 axis, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19657886 we compared the naive immune status of the nasal airway in four different groups of mice including WT, mev, mev crossed with IFN-c KO, and IFN-c KO alone. The nasal airways in mev mice had mild eosinophilic inflammation skewed to the Th2 immune response. In line with the pulmonary findings of the mev mice, SHP-1 deficiency-induced nasal inflammation was down-regulated with