Treg/IL-17 ratio and Treg differentiation in patients with COPD.
Treg/IL-17 ratio and Treg differentiation in patients with COPD.
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COPD患者的Treg/IL-17比值和Treg分化
DOI：
10.1371/journal.pone.0111044
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xin JB
中科院分区：
文献类型：
--
作者：
Jin Y;Wan Y;Chen G;Chen L;Zhang MQ;Deng L;Zhang JC;Xiong XZ;Xin JB
慢性阻塞性肺疾病（COPD）以慢性肺部和全身炎症为特征。异常的适应性免疫反应导致促炎和抗炎过程之间的不平衡。t辅助细胞（Th）、t细胞毒性细胞（Tc）和t调节细胞（Treg）可能在免疫和炎症反应中发挥重要作用。本研究旨在阐明COPD患者，特别是急性加重期（AECOPD）中细胞因子和T淋巴细胞亚群的变化和失衡。本研究纳入了23例稳定型COPD （SCOPD）患者和21例AECOPD患者。此外，20名年龄、性别和体重匹配的不吸烟健康志愿者被纳入对照组。采用酶联免疫吸附试验（ELISA）试剂盒检测血清中选定的细胞因子（TGF-β、IL-10、TNF-α、IL-17、IL-9）水平。用抗cd3 - apc、抗cd4 -PerCP、抗cd8 -PerCP、抗cd25 - fitc和抗foxp3 - pe单克隆抗体染色后，采用流式细胞术检测外周血T淋巴细胞亚群。重要的是，为了消除炎症因子的混杂影响，作者引入了“炎症调节”的概念，并使用代表性炎症标志物（如TNF-α和IL-17）校正了每个测量值。与其他细胞因子不同，无论调整与否，AECOPD患者血清TGF-β水平均明显高于对照组。三组患者CD4+或CD8+ T细胞百分比均无显著差异。急性加重期Tregs虽然相对上调，但其产生和分化能力还远远不够。最后，作者注意到各组之间Treg/IL-17的比率相似。这些观察结果表明，在COPD患者中，特别是在急性加重期间，促炎和抗炎反应都加强，以促炎反应为主。虽然Treg/IL-17比例正常，但调节性T细胞仍不足以抑制伴随的炎症增加。这些变化提示了一种复杂的促抗失衡机制，有待进一步研究。
Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systematic inflammation. An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes. T-helper (Th), T-cytotoxic (Tc) and T-regulatory (Treg) cells may play important roles in immune and inflammatory responses. This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD). Twenty-three patients with stable COPD (SCOPD) and 21 patients with AECOPD were enrolled in the present study. In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls. The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies. Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of “inflammation adjustment” and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17. Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment. There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups. Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient. Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups. These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions are strengthened, with the pro-inflammatory reactions dominating. Although the Treg/IL-17 ratios were normal, the regulatory T cells were still insufficient to suppress the accompanying increases in inflammation. All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated.
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