超表达Serratel树突细胞对支气管哮喘小鼠CD4^＋CD25^＋细胞分化的作用

The effects of dendritic cells overexpressing Serrate1 on the differentiation of CD4^＋ CD25^＋ T cells in asthmatic mice

目的观察超表达Serratel树突细胞（DC）对支气管哮喘（以下简称哮喘）小鼠CD4^＋CD25^＋T细胞极化及抑制性细胞因子分泌的影响。方法将超表达Serratel DC和正常DC在体外用10μg/ml卵蛋白共同培养2h后，从哮喘小鼠尾静脉注射1×10^4DC，再用1％卵蛋白雾化激发，流式细胞仪检测Serratel组和对照组小鼠脾脏CD4^＋CD25^＋T细胞百分率，RT—PCR法检测脾脏CD4^＋T细胞IL-10、转化生长因子β1（TGFβ1）、细胞毒T细胞相关抗原4（CTLA-4）mRNA表达，并观察2组小鼠肺组织的病理学改变。结果与对照组相比，Serratel组可使哮喘小鼠脾脏CD4^＋CD25^＋T细胞数量明显增多，占CD4^＋T细胞的百分数亦明显增高；Serratel组CD4^＋T细胞IL-10、CTLA-4、TGFβ1 mRNA表达明显增强，且气道炎症明显减轻。结论超表达Serratel DC能抑制哮喘小鼠CD4^＋T细胞分化和促进CD4^＋T细胞分泌抑制性细胞因子，有效改善哮喘小鼠气道炎症，表明DC可通过Notch1／Serratel信号通路影响调节性T细胞分化、逆转哮喘免疫耐受缺陷。

Objective To observe the effects of dendritic cells （DCs） overexpressing Serratel on the differentiation of CD4^＋ CD25^＋ T cells and the production of inhibitory cytokines in asthmatic mice. Methods Asthma mouse model was established by the routine method. After intravenous injection of the DCs transfected with Serratel into the naive mice, the airway and lung inflammation was observed and the count of CD4^＋ CD25^＋ T cells delivered from the spleen and the percentage accounting for CD4^＋ T cells were measured by flow cytometry. The expression of IL-10, transforming growth factor （TGF） β1, and cytologic Tlymphocyte-associated antigen （CTLA）-4 mRNA of CD4^＋ T cells were detected by RT-PCR. Results Compared with the non-transfected group, the airway inflammation of asthmatic mice injected the DCs transfected with Serrate1 reduced significantly, the number of CD4^＋ CD25^＋ T cells delivered from the spleen and the percentage accounting for CD4^＋ T cells and the expression of IL-10, TGFβ1, and CTLA-4 mRNA of CD4^＋ T increased. Conclusions DCs overexpressing Serratel could induce the differentiation of the CD4^＋ CD25^＋ T cells and increase the production of inhibitory cytokines in asthma in vivo, indicating that Notchl/Serratel signal pathway of DCs plays an important role in the induction of immune tolerance of T cells to allergens.