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循环中产生白细胞介素-9的CD8 T细胞增加与过敏性哮喘患者的嗜酸性粒细胞增多和呼出一氧化氮水平升高有关。

Increased circulating IL-9-producing CD8 T cells are associated with eosinophilia and high FeNO in allergic asthmatics.

作者信息

Wang Wei, Cheng Zhen-Shun, Chen Yi-Fei, Lin Yu-Hui

机构信息

Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

出版信息

Exp Ther Med. 2016 Dec;12(6):4055-4060. doi: 10.3892/etm.2016.3870. Epub 2016 Nov 3.

Abstract

Allergic asthma is a chronic airway disorder mediated by Th2 cells. It has been shown that IL-9-producing CD8 cytotoxic T (Tc9) cells promote the subsequent onset of allergic airway inflammation in mice mediated by abnormal Th2 immunity. Whether Tc9 cells are associated with the immunopathogenesis of asthmatic patients remains unknown. In the present study, peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque gradient centrifugation from all subjects. The frequency of Tc9 cells was measured by flow cytometry. Serum IL-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). mRNA expression levels of IL-9, STAT6, and IRF4 in PBMCs from healthy controls and asthmatic patients were detected by reverse transcription-quantitative polymerase chain reaction. The results showed that the numbers of Tc9 cells in allergic asthmatics were significantly increased, compared with healthy controls (P<0.0001). Notably, IL-9 protein and mRNA levels were increased in allergic asthmatics and STAT6 and IRF4 mRNA levels were elevated, as compared with healthy controls. In addition, circulating numbers of Tc9 cells were positively correlated with blood eosinophil counts and fractioned exhaled nitric oxide (FeNO) levels in asthmatic patients. Moreover, the number of Tc9 cells and serum IL-9 levels in asthmatic patients were significantly decreased after treatment with glucocorticoids (P<0.05). These findings suggest that increased circulating Tc9 cells are associated with eosinophilia and high FeNO of allergic asthma, and that abnormal Tc9 immunity may contribute to the pathogenesis of allergic asthmatics.

摘要

过敏性哮喘是一种由Th2细胞介导的慢性气道疾病。研究表明,产生白细胞介素-9(IL-9)的CD8细胞毒性T细胞(Tc9细胞)可促进小鼠体内由异常Th2免疫介导的过敏性气道炎症的后续发作。Tc9细胞是否与哮喘患者的免疫发病机制相关尚不清楚。在本研究中,通过Ficoll-Hypaque梯度离心法从所有受试者中分离出外周血单核细胞(PBMC)。通过流式细胞术检测Tc9细胞的频率。采用酶联免疫吸附测定(ELISA)评估血清IL-9水平。通过逆转录定量聚合酶链反应检测健康对照和哮喘患者PBMC中IL-9、信号转导和转录激活因子6(STAT6)以及干扰素调节因子4(IRF4)的mRNA表达水平。结果显示,与健康对照相比,过敏性哮喘患者的Tc9细胞数量显著增加(P<0.0001)。值得注意的是,与健康对照相比,过敏性哮喘患者的IL-9蛋白和mRNA水平升高,STAT6和IRF4的mRNA水平也升高。此外,哮喘患者循环中的Tc9细胞数量与血液嗜酸性粒细胞计数和呼出一氧化氮分数(FeNO)水平呈正相关。而且,哮喘患者经糖皮质激素治疗后,Tc9细胞数量和血清IL-9水平显著降低(P<0.05)。这些发现表明,循环中Tc9细胞增加与过敏性哮喘的嗜酸性粒细胞增多和高FeNO相关,且异常的Tc9免疫可能参与过敏性哮喘的发病机制。

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