A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps

Abstract

Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG 1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs. Clinical RelevanceThe present study demonstrates that the nasal polyp (NP) mouse model revealed enhanced B cell responses, reminiscent of human NPs. This mouse model may enhance our understanding of the pathophysiology of NPs and provide a model to test therapeutic targets in vivo.Chronic rhinosinusitis (CRS) is one of most common chronic diseases worldwide. CRS can be categorized into two types: CRS with nasal polyps (NPs; CRSwNPs) and CRS without NPs (CRSsNPs). The pathogenesis of NPs is incompletely understood, and lack of an in vivo animal model for NPs has been a major hurdle in investigating NP pathogenesis and testing new treatment modalities. Animal model systems are invaluable in vivo models for examining a variety of human diseases and aid in the

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Animal Models in CRS and Pathophysiologic Insights Gained: A Systematic Review

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Role of IL‐13Rα2 in modulating IL‐13‐induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa

“…To confirm and fully investigate IL‐13Rα2's mechanism that contributes to polypogenesis, future experiments using IL‐13Rα2 knockout or overexpression cell or animal models can be employed to observe their responses to IL‐13 leading to subsequent polypogenesis and its associated features. Additionally, the knockout of IL‐13Rα2 using antibodies or locked nucleic acid (LNA) RNAi strategies could be further applied to a recently established mouse nasal polyp model to observe IL‐13Rα2's role in accelerating polyp formation…”