Effects of recombinant IL-35-BCG neonatal inoculation on Tregs/Th17 balance in experimental asthma model
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摘要: 目的 建立重组卡介苗(recombinant Bacillus Calmette-Guérin,rBCG)新生期接种的小鼠哮喘模型,观察生命早期进一步加强Tregs类免疫反应后,哮喘发作阶段气道炎症受到的干预作用及其机制。 方法 清洁级BALB/c新生小鼠随机分为3组:IL-35-BCG组、OVA组、对照组,IL-35-BCG组新生期接种后分别在生后第4周和第6周进行OVA致敏,OVA组新生期给予BCG稀释液(不含BCG)接种后分别在生后第4周和第6周进行OVA致敏,除对照组外小鼠哮喘模型均在第7周开始使用OVA激发,连续激发1周,最后一次激发后24 h内,进行相关检测。 结果 IL-35-BCG组与OVA组支气管肺泡灌洗中白细胞总数、嗜酸性粒细胞、淋巴细胞、中性粒细胞等比例都比对照组明显升高,而IL-35-BCG组上述细胞均显著低于OVA组。流式细胞术显示IL-35-BCG组与OVA组肺部Tregs细胞比例均明显高于对照组(均P<0.05),且与OVA组相比,IL-35-BCG新生期接种组哮喘小鼠Tregs细胞比率明显升高,差异有统计学意义(P<0.05)。IL-35-BCG组与OVA组肺部Th17细胞比例均明显高于对照组(均P<0.05),但与OVA激发的哮喘组比较,新生期IL-35-BCG接种小鼠激发后Th17细胞比例明显降低,差异有统计学意义(P<0.05)。 结论 新生期接种IL-35-BCG在哮喘期,促进Tregs分化,抑制Th17细胞分化,明显减轻哮喘小鼠模型气道炎症细胞浸润。提示Tregs及Th17细胞在实验性哮喘小鼠发病中起作用,新生期接种IL-35-BCG在生命早期增强Tregs介导的免疫应答,以便诱导Tregs细胞在发生哮喘时发挥抗哮喘作用。Abstract: Objective To observe the effects of recombinant IL-35-BCG(rBCG) neonatal inoculation on Tregs/Th17 balance in experimental asthma model. Methods We divided Neonatal BALB/c mice into 3 groups: IL-35-BCG, OVA and control groups. Within 2-3 days after birth, mice in IL-35-BCG group were inoculated with IL-35-BCG subcutaneously. At 4-week and 6-week, using the intraperitoneal OVA with alum sensitization protocol as mice in OVA group. Mice were used to perform asthma model and were challenged by an aerosol of OVA at 7- week for one week. Within 24 hours after the last atomization, the proportion of Th17 cells and Tregs cells was detected by flow cytometry. Results After sensitization, the proportion of Th17 cells and Tregs cells were no significant difference between the neonatal IL-35-BCG group and OVA group. After stimulation, the percentage of Th17 cells in IL-35-BCG group was significantly lower than in OVA group, while the percentage of Tregs cells was significantly higher than that in OVA group. Conclusion Tregs in IL-35-BCG group is significantly higher than those in OVA group and control group after stimulation, while the proportion of TH17 cells is significantly lower in the IL-35-BCG group than those in the other two groups. This further indicates that the anti-asthmatic effect of neonatal IL-35-BCG vaccination is mainly through changing Tregs/Th17 balance.
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Key words:
- Recombinant BCG /
- Asthma model /
- T cell subgroups
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