OX40基因对卵清白蛋白诱导的小鼠哮喘模型的影响机制研究

Study on the mechanism of OX40 in mice with OVA-induced allergic asthma

目的研究OX40基因对卵清白蛋白(OVA)诱导的小鼠哮喘模型中的影响及其机制。方法选取6~8周龄雄性C57/BL6小鼠20只,应用腹腔注射OVA致敏和雾化吸入OVA的方式诱导野生型和OX40基因敲除小鼠产生过敏性哮喘。通过苏木精-伊红染色、迪夫快速染色、肺气道呼吸阻力测试等方法验证哮喘疾病严重程度。通过流式细胞术检测肺泡灌洗液和肺实质中嗜酸性粒细胞、CD4 T细胞、滤泡辅助T(Tfh)细胞和CD11b^+CD8^-树突状细胞亚群比率。结果OX40基因敲除明显减轻了OVA诱导的小鼠过敏性哮喘的疾病症状和嗜酸性粒细胞在肺部的浸润。与野生型哮喘小鼠相比,OX40基因敲除的哮喘小鼠肺脏中CD4 T细胞和Tfh细胞亚群比率明显降低,CD11b^+CD8^-树突状细胞比率也明显降低。结论OX40基因促进了OVA诱导的小鼠哮喘疾病进程,并显著增高了Tfh细胞和CD11b^+CD8^-树突状细胞比率。

Objective To study the regulation of OX40 in OVA-induced allergic mouse asthma.Methods A total of wildtype and OX40 KO mice were sensitized by intraperitoneal injection of OVA protein and they were exposed to aerosolized OVA.The pathological examination of tissue sections was detected by hematoxylin-eosin staining,Diff-Quik staining and airway hyperreactivity plethysmography.Flow cytometry was applied to detect proportion of eosinophils,CD4 T cells,T follicular helper(Tfh)cells and CD11 b^+CD8^-dendritic cells in bronchoalveolar lavage fluid and lung.Results OX40 knockout ameliorate symptoms and eosinophil accumulation in OVA-induced allergic asthma.In comparison with wildtype mice,the proportion of CD4 T cells,T follicular helper cells and CD11 b^+CD8^-dendritic cells were significantly decreased in OX40 KO mice.Conclusion OX40 knockout ameliorate the disease progress and decrease the proportion of T follicular helper cells and CD11 b^+CD8^-dendritic cells in mice with OVA-induced allergic asthma.