评估调节性T细胞/辅助性T细胞17轴在芥子气肺病慢性损伤免疫发病机制中的作用。
Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease.
作者信息
Imani Saber, Salimian Jafar, Bozorgmehr Mahmood, Vahedi Ensieh, Ghazvini Ali, Ghanei Mostafa, Panahi Yunes
机构信息
a Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran and.
b Department of Immunology , Ebn-e-Sina Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
出版信息
J Recept Signal Transduct Res. 2016 Oct;36(5):531-41. doi: 10.3109/10799893.2016.1141953. Epub 2016 Feb 19.
PURPOSE
Sulfur mustard (SM) lung is a heterogeneous disease associated with abnormal inflammatory immune responses. The Th17/Treg axis imbalance is associated with the pathogenesis of chronic inflammatory pulmonary disease. We aimed to determine the distribution of different Th17 and Treg cells in patients with SM lung and chronic obstructive pulmonary disease (COPD) and evaluate the clinical implications in this homeostasis.
METHODS
In this analytical cross-sectional study, CD4 (+) Foxp3(+ )Treg and CD4(+) IL-17(+ )Th17 cells were measured in peripheral blood mononuclear cells (PBMCs) and transbronchial biopsy (TBB) samples of 15 SM-exposed patients, 12 COPD and 13 healthy controls (HCs). The potential correlation between the ratio of Th17/Tregs and lung function was evaluated with multivariate logistic regression (MLR) analysis.
RESULTS
The frequency of CD4 (+) FoxP3(+) Tregs and CD4 (+) IL-17(+) Th17 was increased ∼1.7-fold (8.71/4.95) and ∼2.7-fold (1.028/0.371) respectively, in the PBMC of SM patients compared with the health controls (p < 0.001). The results indicated that there were increases in the frequency of Th17 and Tregs cells in the patients with COPD versus the HC, that is, ∼2.6-fold (0.987/0.371) and ∼1.4-fold (7.12/4.95), respectively; but they did not reach to SM level (p ≥ 0.05). Moreover, in the TBB samples, the CD4 (+) IL-17(+ )Th17 and CD4(+) FoxP3(+ )Tregs numbers were significantly higher in SM and COPD patients than HC (p < 0.05). The Th17 and Treg cells were inversely correlated with forced expiratory volume in 1s (FEV1%) (r = -0.351, p = 0.001; r = -0.344, p = 0.021) and FEV1/FVC (r = -0.44, p = 0.001; r = -0.302, p = 0.011), respectively. Instead, positive correlations were found between Treg/Th17 ratios and forced FEV1%pred (r = 0.156, p = 0.007), as well as FEV1/FVC ratio (r = 0.334, p = 0.006).
CONCLUSIONS
The imbalance of Th17/Treg has a key role in immunopathogenesis of chronic phase of mustard lung disease.
目的
硫芥（SM）肺是一种与异常炎症免疫反应相关的异质性疾病。Th17/Treg轴失衡与慢性炎症性肺病的发病机制有关。我们旨在确定SM肺患者和慢性阻塞性肺疾病（COPD）患者中不同Th17和Treg细胞的分布，并评估这种内环境稳态的临床意义。
方法
在这项分析性横断面研究中，对15名接触过SM的患者、12名COPD患者和13名健康对照者（HCs）的外周血单个核细胞（PBMCs）和经支气管活检（TBB）样本中的CD4(+)Foxp3(+)Treg和CD4(+)IL-17(+)Th17细胞进行了检测。采用多因素逻辑回归（MLR）分析评估Th17/Tregs比值与肺功能之间的潜在相关性。
结果
与健康对照相比，SM患者PBMC中CD4(+)FoxP3(+)Tregs和CD4(+)IL-17(+)Th17的频率分别增加了约1.7倍（8.71/4.95）和约2.7倍（1.028/0.371）（p<0.001）。结果表明，与HC相比，COPD患者中Th17和Tregs细胞的频率增加，分别约为2.6倍（0.987/0.371）和约1.4倍（7.12/4.95）；但未达到SM患者的水平（p≥0.05）。此外，在TBB样本中，SM和COPD患者的CD4(+)IL-17(+)Th17和CD4(+)FoxP3(+)Tregs数量显著高于HC（p<0.05）。Th17和Treg细胞分别与第1秒用力呼气量（FEV1%）呈负相关（r=-0.351，p=0.001；r=-0.344，p=0.021）和FEV1/FVC呈负相关（r=-0.44，p=0.001；r=-0.302，p=0.011）。相反，Treg/Th17比值与预计FEV1%（r=0.156，p=0.007）以及FEV1/FVC比值呈正相关（r=0.334，p=0.006）。
结论
Th17/Treg失衡在芥子气肺病慢性期的免疫发病机制中起关键作用。
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