Tim-3在哮喘小鼠中的表达及与Th17/Treg细胞的关系  

Expression of Tim-3 and its relationship with Th17 / Treg cytokine in the peripheral blood and airway in asthmatic murine

作　　者：王艳丽[1] 陆小霞[1] 陈鹏[1] 陈和斌[1] 王莹[1] 

机构地区：[1]武汉市妇女儿童医疗保健中心呼吸内科,430016

出　　处：《实用医学杂志》2015年第7期1095-1098,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金青年科学基金项目(编号:81200006);吴阶平医学基金项目(编号:320.6750.1285);湖北省自然科学基金项目(编号:2010CDB08804);武汉市卫生局科研项目(编号:WX11B10)

摘　　要：目的 :检测支气管哮喘小鼠外周血单个核细胞(PBMC)及肺泡灌洗液(BALF)炎性细胞中T细胞免疫球蛋白与黏蛋白域蛋白3(Tim-3)的表达及与Th17/Treg细胞的关系,探讨其在哮喘发病中的作用。方法 :建立小鼠哮喘动物模型,分为哮喘组和对照组。收集各组小鼠PBMC及BALF炎性细胞,应用实时荧光定量PCR检测PBMCs及BALF炎性细胞中的Tim-3 m RNA水平,流式细胞仪检测CD4细胞中IL-17(CD4+IL-17+)比例反映Th17水平,CD4细胞中CD4+CD25+Fox P3+反映Treg细胞水平;酶联免疫吸附法(ELISA)检测PBMCs上清液中IL-10、IL-17、TGF-β水平,分析Tim-3的表达与Th17/Treg水平的相关性。结果:哮喘组PBMCs及BALF炎性细胞中Tim-3 m RNA水平、CD4+IL-17+表达及Th17/Treg比例、IL-17均高于对照组(P<0.05),而CD4+CD25+Fox P3+水平、IL-10显著低于对照组。哮喘组PBMCs及BALF炎性细胞中的Tim-3 m RNA表达分别与CD4+IL-17+表达及Th17/Treg比例呈正相关(r=0.76,r=0.87,r=0.71,r=0.82,P<0.05),而与CD4+CD25+Fox P3+的表达呈负相关(r=-0.84,r=-0.79,P<0.05)。结论:哮喘小鼠PBMCs及BALF炎性细胞中Tim-3 m RNA水平显著升高,Tim-3可能在哮喘发生发展中起着重要作用并与Th17/Treg失衡有关。Objective To detect the expression of T cell immunoglobulin mucin 3 （Tim-3） and its relationship with Thl7/Treg cytokine isolated from peripheral blood mononuclear cells （PBMCs） and broncho- alveolar lavage fluids （BALF） cells in the asthmatic routine model and to investigate the role of Tim-3 in the occurrence and development of the asthmatic inflammation. Methods The asthmatic routine model was established by the method of ovalbumin （OVA） injection and inhalation. The mice were randomly divided into 2 groups： the normal control and the asthma group. PBMCs and BALF cells in each group were collected. Expression of Tim-3 mRNA was detected by the real-time PCR assay. Levels of CD4＋IL-17＋ and CD4＋CD25＋ FoxP3＋, reflecting expressions of Thl7 and Treg respectively, were detected by flow cytometry. The correlation between Tim-3 and Thl7/Treg level was analyzed. Results Contrast with the normal control group, the expression of Tim-3 mRNA in PBMCs and BALF cells in the asthma group increased significantly （P 〈 0.01 ）. OVA sensitization and challenges resulted in the increased CD4＋IL-17 production and the decreased CD4＋CD25＋Foxp3＋ in PBMCs and BALF cells compared with those in the normal control group （both P 〈 0.05）. The ratio of ThlT/ Treg significantly increased in asthma group （P 〈 0.05 ）. Tim-3 mRNA expression in PBMCs and BALF cells was positively correlated with CD4＋IL-17＋ level and Thl7/Treg ratio, respectively, and was negatively correlated with CD4＋CD25＋Foxp3＋ level. Conclusions Tim-3 mRNA level in PBMCs and BALF cells in the asthma group was increased, indicating that Tim-3 might take part in the occurrence and development of asthmatic inflammation and has a very close relationship with the Thl7/Treg imbalance.

关 键 词：哮喘 T淋巴细胞 TIM-3 TH17/TREG 

分 类 号：R562.25[医药卫生—呼吸系统]