TIM-3介导免疫平衡失调与支气管哮喘发病的意义及机制研究

Relationship betweenTim-3 mediated immune imbalance and bronchial asthma

目的：探讨TIM-3介导免疫平衡失调与支气管哮喘发病的意义及机制。方法：选取2013年1月~2014年6月在本院呼吸科就诊并诊断为支气管哮喘患者及正常健康人设为实验组和对照组,各50例,收集外周血,流式细胞仪检测两组人群外周血中辅助性T细胞17（T helper 17,Th17）及调节性T细胞（regulatory T cell,Treg细胞）比例,并检测TIM-3表达改变,分析其与支气管哮喘发病的相关性;并阻断TIM-3表达,观察其对Th17及Treg细胞的影响。结果：Tim-3抑制前,实验组患者Th17、Treg细胞比例以及Th17/treg值均高于对照组患者,差异有统计学意义（P〈0.01）;Tim-3抑制后,实验组患者Th17细胞比例和Th17/treg值仍高于对照组患者,差异有统计学意义（P〈0.01）,而Treg细胞比例和对照组无显著差别（P〉0.01）;Tim-3抑制前后,实验组患者Th17、Treg细胞比例以及Th17/treg值均有显著变化,差异有统计学意义（P〈0.01）。相关性分析的结果表明外周血中Th17细胞比例同Treg细胞为负相关关系（r=-0.436,P〈0.05）。实验组及对照组患者外周血中CD4＋Tim3＋细胞占CD4＋细胞比例分别是（5.22±0.95）%和（2.20±0.41）%,实验组显著高于对照组,差异具有统计学意义（P〈0.01）。对照组患者Th17细胞有少量Tim-3[（0.18±0.05）%]表达,实验组患者外周血中Th17细胞基本无Tim-3表达,两组差异无统计学意义（P〉0.05）。结论：哮喘患者外周血中Th17细胞和Treg细胞比例失衡,可能为哮喘发生的重要诱导因素,Tim-3抑制后,实验组患者Th17细胞和Treg细胞比例有显著变化,暗示Tim-3的表达对这两种细胞数量有明显的调控作用。此外支气管哮喘患者外周血T淋巴细胞中TIM-3表达有显著增高。

Objective：To explore relationship betweenTim-3mediated immune imbalance and bronchial asthma.Methods：A total of 50 patients with bronchial asthma during 2013.1to 2014.6in our hospital were selected as the experimental group and other 50 healthy people were selected as the control group.Peripheral blood was collected and Th17 and Treg cells ratio in peripheral blood were detected by flow cytometry,the changes of Tim-3expression was also detected and its relevance with bronchial asthma was explored.Then the Tim-3expression was blocked and its influence on Th17 and Treg cells was observed.Results：Before Tim-3blocked,the cell ratio of Th17 and Treg cells and Th17/treg values in experimental were significantly higher than that of control group（P〈0.01）;After Tim-3blocked,the cell ratio of Th17 and Th17/treg values in experimental were still significantly higher than that of control group（P〈0.01）,while the difference in cell ratio of Treg cells was not statistically significant.Before and after Tim-3inhibition,Th17,Treg cell ratio and Th17/treg value of experimental group showed significant changes（P〈0.01）.Correlation analysis results showed that the proportion of Th17 cells with Treg cells in peripheral blood were negatively correlated（r=-0.436,P〈0.05）.CD4＋Tim3＋cells in CD4＋cell percentage of experimental group and control group were（5.22±0.95）%and（2.20±0.41）%respectively,with significant difference（P〈0.01）.Th17 cells of control group showed low Tim-3（0.18 ± 0.05）% expression in peripheral blood and no expression in experimental group.The difference was not statistically significant（P〉0.05）.Conclusion：The imbalance of Th17 and Treg cells in peripheral blood of patients with asthma may be an important factor to induce asthma.After Tim-3inhibition,the Th17,Treg cell ratio of experimental group show significant changes,which suggests that Tim-3expression have significant regulatory function of the number of these two cells.Also the TIM-3expression in T lymphocytes was significantly increased in patients with bronchial asthma.