γδ T 细胞 T 细胞受体库基因表达谱及白细胞介素-17A 基因在急性心肌梗死患者中的改变表达。
Gene expression pattern of TCR repertoire and alteration expression of IL-17A gene of γδ T cells in patients with acute myocardial infarction.
机构信息
Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
Institute of Hematology, Jinan University, Guangzhou, 510632, China.
出版信息
J Transl Med. 2018 Jul 5;16(1):189. doi: 10.1186/s12967-018-1567-7.
BACKGROUND
γδ T cells are associated with the pathogenesis of coronary atherosclerotic heart disease, but the relationship between the development of acute myocardial infarction (AMI) and γδ T cells is not clear. So we attempt to investigate the expression pattern and clonality of T cell receptor (TCR) repertoire of γδ T cells in AMI patients, analyze the expression levels of regulatory genes Foxp3 and IL-17A, and characterize the correlation between γδ T cells and the pathogenesis of AMI.
METHODS
25 patients diagnosed with ST-segment-elevation AMI were enrolled and 14 healthy individuals were recruited as the controls. RT-PCR and GeneScan were used to analyze the complementarity-determining region 3 sizes of TCR γδ repertoire genes in sorted γδ T cells from peripheral blood mononuclear cells (PBMCs). RQ-PCR was used to detect the gene expression levels of Foxp3, IL-17A and TCR Vγ subfamilies in sorted γδ T cells. All the patients were followed up for recordings of clinical endpoints.
RESULTS
The mRNA gene expression levels of TCR Vγ1, Vγ2, and Vγ3 subfamilies in AMI patients were significantly higher than those in healthy controls. The expression pattern was Vγ1 > Vγ2 > Vγ3 in AMI patients, while Vγ1 > Vγ3 > Vγ2 in healthy controls. The significantly restricted expression of TCR Vδ subfamilies were also found in AMI patients. The expression frequencies of TCR Vδ7 and TCR Vδ6 in AMI patients were significantly lower than those in healthy controls. The high clonal expansion frequencies of the TCR Vδ8, Vδ4 and Vδ3 were determined in AMI patients. High expression of Foxp3 gene was found in AMI PBMCs, while high expression of IL-17A was found in AMI γδ+ cells.
CONCLUSIONS
Restrictive expression of TCR γδ repertoire and alteration expression of IL-17A gene are the important characteristics of γδ T cells in AMI patients, which might be related to the immune response and clinical outcome. γδ T cells might play a key role in the pathological progress of AMI and associated with the IL-17A mediated pathway.
背景
γδ T 细胞与冠状动脉粥样硬化性心脏病的发病机制有关，但急性心肌梗死（AMI）的发展与 γδ T 细胞之间的关系尚不清楚。因此，我们试图研究 AMI 患者 γδ T 细胞 T 细胞受体（TCR） repertoire 的表达模式和克隆性，分析调节基因 Foxp3 和 IL-17A 的表达水平，并描述 γδ T 细胞与 AMI 发病机制之间的相关性。
方法
纳入 25 例经 ST 段抬高型 AMI 诊断的患者，并招募 14 名健康个体作为对照。使用 RT-PCR 和 GeneScan 分析外周血单个核细胞（PBMCs）中分离的 γδ T 细胞的 TCR γδ repertoire 基因的互补决定区 3 大小。使用 RQ-PCR 检测分离的 γδ T 细胞中 Foxp3、IL-17A 和 TCR Vγ 亚家族的基因表达水平。所有患者均进行临床终点随访记录。
结果
AMI 患者 TCR Vγ1、Vγ2 和 Vγ3 亚家族的 mRNA 基因表达水平明显高于健康对照组。表达模式为 AMI 患者中 Vγ1>Vγ2>Vγ3，而健康对照组中 Vγ1>Vγ3>Vγ2。在 AMI 患者中还发现 TCR Vδ 亚家族的表达明显受限。AMI 患者 TCR Vδ7 和 TCR Vδ6 的表达频率明显低于健康对照组。在 AMI 患者中确定了 TCR Vδ8、Vδ4 和 Vδ3 的高克隆扩增频率。在 AMI PBMCs 中发现 Foxp3 基因高表达，而在 AMI γδ+细胞中发现 IL-17A 基因高表达。
结论
TCR γδ repertoire 的限制性表达和 IL-17A 基因的改变表达是 AMI 患者 γδ T 细胞的重要特征，这可能与免疫反应和临床结局有关。γδ T 细胞可能在 AMI 的病理进展中发挥关键作用，并与 IL-17A 介导的途径有关。
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