耐受性树突状细胞对哮喘小鼠气道变应性炎症反应的抑制作用

Inhibition of mice airway allergic inflammation by inoculation of tolerogenic dendritic cells

目的：用卵白蛋白（OVA）刺激的未成熟树突状细胞（immature dendritic cell,imDC）免疫小鼠,观察其对小鼠OVA激发的气道过敏性炎症反应的抑制作用,探讨耐受性树突状细胞疫苗诱导免疫耐受的可能机制,为临床防治哮喘提供新的思路。方法：制备BALB/c小鼠髓性imDC。其余BALB/c小鼠分4组,10只/组：其中两组于第-7天分别注射无菌PBS（PBS组）、OVA刺激的imDC（imDC组）,第三组于第13~20天注射地塞米松（地塞米松组）,第四组不作任何处理（健康对照组）;除健康对照组外,其余各组诱导哮喘反应：第0天和第9天分别注射OVA致敏,14~20天每日予OVA气雾攻击。第21天每组处理5只小鼠,检测肺部炎症细胞浸润及嗜酸性粒细胞比例、气道黏液分泌、脾细胞Th1/Th2型细胞因子表达及脾细胞中CD4^＋CD25^＋细胞比例;第49天,处理剩余动物,观察哮喘预后。结果：mDC注射组肺部炎症浸润较轻,脾细胞表达白细胞介素（IL）-13、4降低而γ-干扰素（IFN-γ）无显著影响,脾细胞中CD4^＋CD25^＋细胞比例较高,气道黏液分泌则少于PBS组,且预后良好。结论：过敏原特异性imDC疫苗注射可在一定程度上缓解哮喘小鼠气道的变应性炎症反应。

Objective： To investigate whether inoculation of ovalbumin（OVA）-pulsed immature dendritic cells（imDCs） can block mice OVA-induced Th2 pathogenesis in the lung.Methods：（1）ImDCs of BALB/c mice were prepared from bone marrow as tolerogenic DCs.（2）BALB/c mice were divide into 4 groups,10 in each group.7 days before（day-7） OVA sensitization,the PBS group,the imDCs group were injected sterile PBS and OVA-pulsed imDCs,respectively;While mice of the dexamethasone（DXM） group were injected dexamethasone daily from day 13 to 20;Control group mice were kept intact until sacrifice.Mice were sensitized by injection of OVA on day 0 and day 9.From day 14 to day 20,they were challenged intratracheally（i.t） with 1% OVA in saline aerosols daily.（3）On day 21,5 mice of each group were sacrificed.The effect of imDCs on the airway inflammation in sensitized mice were studied.Samples of the remainder mice were collected on day 49 to test prognosis of the disease. Results： Infiltration of inflammatory cells into the lung and proportion of eosinophils（Eos） were notably reduced by injection of imDCs;The immunization protocol also inhibited airway mucosa production and overexpression of Th2 type cytokine interleukin（IL）-13 and 4 in mice models of asthma.However,All animals received imDCs had increased ratio of splenic CD4^＋CD25^＋ cells as well as favorable prognoses. Conclusion： Inoculation of tolerogenic DC was a potential method to inhibit airway inflammation in mice models via reducing Th2 response and inducing peripheral T regulatory cells.