Wang Huaying, Ying Huajuan, Wang Shi, Gu Xiao, Weng Yuesong, Peng Weidong, Xia Dajing, Yu Wanjun
Department of Respiratory and Critical Care Medicine, The Affiliated Yinzhou Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, China.
Clinical Laboratory, The First Hospital, Ningbo, Zhejiang, China.
Clin Respir J. 2015 Jul;9(3):330-41. doi: 10.1111/crj.12147. Epub 2014 May 21.
Autoimmune responses mediated by cluster of differentiation 4(+) T cells may contribute to the development of chronic obstructive pulmonary disease (COPD). However, little is known about the frequency of peripheral blood Th17 cells and of regulatory T cells (Tregs) in Chinese patients with COPD. This study is aimed at determining the frequency of circulating Th17 and Tregs in patients with moderate and severe COPD, heavy smokers and healthy controls (HC).
The percentages of circulating T-helper type (Th)17 cells and Tregs were determined by flow cytometry in 32 patients with moderate COPD, 33 patients with severe COPD, 35 smokers, and 31 HC. The concentrations of serum Th17- and Treg-related cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The levels of retinoic acid orphan receptor (ROR)-γt and Forkhead box p3 (Foxp3) mRNA transcripts in peripheral blood mononuclear cells were determined by real-time polymerase chain reaction. The potential correlation between the percentages of Th17 Tregs, serum cytokines and lung function was evaluated.
In comparison with that in the smokers and HC, significantly higher frequencies of Th17 cells and higher levels of ROR-γt mRNA transcripts and serum interleukin (IL)-17A, IL-6, IL-21, IL-22 and IL-23, but lower frequency of Tregs and lower levels of Foxp3 and serum IL-10 were detected in patients with moderate and severe COPD. The increased ratios of Th17 to Tregs were negatively correlated with the values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC.
An imbalance of circulating Th17 cells and Tregs is associated with the deterioration of pulmonary function in patients with moderate and severe COPD.
由分化簇4(+)T细胞介导的自身免疫反应可能促使慢性阻塞性肺疾病(COPD)的发展。然而,对于中国COPD患者外周血Th17细胞和调节性T细胞(Tregs)的频率了解甚少。本研究旨在确定中度和重度COPD患者、重度吸烟者及健康对照者(HC)循环中Th17细胞和Tregs的频率。
采用流式细胞术测定32例中度COPD患者、33例重度COPD患者、35例吸烟者和31例HC循环中辅助性T细胞(Th)17细胞和Tregs的百分比。采用酶联免疫吸附测定(ELISA)法检测血清Th17和Treg相关细胞因子的浓度。通过实时聚合酶链反应测定外周血单个核细胞中维甲酸孤儿受体(ROR)-γt和叉头框p3(Foxp3)mRNA转录本的水平。评估Th17、Tregs百分比、血清细胞因子与肺功能之间的潜在相关性。
与吸烟者和HC相比,中度和重度COPD患者Th17细胞频率显著更高,ROR-γt mRNA转录本及血清白细胞介素(IL)-17A、IL-6、IL-21、IL-22和IL-23水平更高,但Tregs频率更低,Foxp3及血清IL-10水平更低。Th17与Tregs的比值升高与用力肺活量(FVC)、第1秒用力呼气容积(FEV1)及FEV1/FVC值呈负相关。
循环中Th17细胞和Tregs失衡与中度和重度COPD患者肺功能恶化相关。