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Let-7a在哮喘T淋巴细胞失衡中的作用研究

The Function of Let-7a in the Imbalance of T Cell in Asthma
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摘要 目的:探讨let-7a在哮喘中的表达水平及调节T淋巴细胞亚群失衡的功能作用.方法:收集39例哮喘患者及19例非哮喘对照,Real-time PCR检测let-7a的表达.从哮喘患者外周血单核细胞(Peripheral blood mononuclear cell,PBMC)中分选Th1,Th2和Th17细胞,检测let-7a在T淋巴细胞亚群中的表达.磁珠分选naive T细胞,分别诱导分化成Thl、Th2和Thl7细胞,分析let-7a在T淋巴细胞亚群中的表达.Let-7amimic分别转染Th2和Th17细胞,ELISA检测IL-13和IL-17的表达.结果:与对照组比较,let-7a在哮喘患者肺组织和血清中低表达,并随着哮喘病程进展,let-7a的表达水平也越低.哮喘患者来源的CD4^+T细胞中,let-7a表达明显低于非哮喘对照组.Let-7a在哮喘来源和体外刺激分化的哮喘炎性Th2和Th17细胞中的表达明显下调,而在Thl细胞中的表达没有变化.Let-7a mimic改变了Th2和Th17相关细胞因子IL-13和IL-17的表达.结论:Let-7a在哮喘中低表达,调节哮喘T淋巴细胞亚群失衡,改变了Th2和Th17细胞的功能,是哮喘理想的诊断和治疗靶点. Objective:To analyze let-7a expression in patients with asthma and explore the bio-function of let-7a on the imbalance ofT cell subsets in asthma.Methods:39 patients with asthma and 19 non-asthma control were recruited in this research.The expression oflet-7a was analyzed using Real-time PCR.The naive T cells were separated with magnetic beads,and then differentiated into Th1,Th2 and Th17 cells under cytokines stimulation in vitro,respectively.IL-13 and IL-17 were further detected with ELISA after let-7a mimic was transfected into Th2 and Th17 cells.Results:Compared with control group,let-7a was down-regulated in lung tissue and serum in patients with asthma.At the same time,the expression oflet-7a was decreased with the development of asthrna progression.Furthermore,let-7a expression was decreased in CD4+ cells in patients with asthma than that in control group.Interestingly,let-7a was significantly down-regulated in Th2 and Th17 ceils from either patients with asthma or the differentiation in vitro,whereas let-7a expression had no significant change in Thl cells.Let-7a inhibited IL-13 secretion in Th2 and IL-17 in Th17 cells,respectively,indicating that let-7a had an important role on the function of Tb2 and Thl7 cells.Conclusions:Down-expressing let-7a in asthma regulated the imbalance of T cell subsets and altered the function of Th2 and Thl7 cells.Thus,let-7a may be an ideal bio-marker for asthma diagnosis and therapy.
作者 段明明 吴守振 李海龙 杨玉琮 DUAN Ming-yue, WU Shou-zhen, LI Hai-long, YANG Yu-cong (1 Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; 2 The Second Department of Genatn'cs, Ninth Hospital of Xi'an, Xi'an, Shaanxi, 710048, China; 3 Department of Clinical Laboratory, the First Aflfliated Hospital ofXi'an Jiaotong University, Xi'an, Shaanxi, 710061, China)
出处 《现代生物医学进展》 CAS 2017年第15期2829-2832,共4页 Progress in Modern Biomedicine
基金 陕西省自然科学基础研究计划项目(2016JM8096)
关键词 Let-7a 哮喘 生物标志物 Let-7a Asthma Biomarker
作者简介 段明碉(1984-),硕士研究生,助理研究员,主要研究方向:免疫学,E—mail:dmy117@163.com 通讯作者:杨玉琮,博士研究生,硕士生导师,主任医师,主要研究方向:临床免疫学诊断技术及方法学研究,E-mail:yyc1103@mail.xjtu.edu.cn,电话:029-85323502
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