Su Zhaoliang, Lu Hongxiang, Jiang Haiqiang, Zhu Haitao, Li Ze, Zhang Pan, Ni Ping, Shen Huiling, Xu Wenlin, Xu Huaxi
The Central Laboratory, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China; Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
Atherosclerosis. 2015 Dec;243(2):421-8. doi: 10.1016/j.atherosclerosis.2015.09.037. Epub 2015 Oct 3.
IFN-γ-producing Th17 cells have been implicated in autoimmune disorders, but their properties in humans are known only partially. The molecular mechanisms and external factors that govern IFN-γ-producing Th17-cell bias are incompletely understood. The present work was to clarify whether (i) IFN-γ-producing Th17 cells are present in the peripheral circulation of patients with coronary atherosclerosis (CA); (ii) high mobility group box (HMGB)1 in circulation is associated with IFN-γ-producing Th17-cell bias.
Thirty-six patients (17 females and 19 males; 45-84 years) diagnosed as having atherosclerosis after coronary angiography for suspected or known CA were included the study cohort. Samples of peripheral blood were collected from healthy volunteers and patients, and classical tests (flow cytometry, RT-qPCR) were used to measure blood components.
Our results clearly demonstrated that HMGB1 were up-regulated in different progressive CA patients: 5.38 ± 1.48 ng/ml, 6.30 ± 1.53 ng/ml and 5.86 ± 1.12 ng/ml vs1.45 ± 0.65 ng/ml for only atherosclerotic plaque (AP), atherosclerotic plaque and some plaque rupture, no thrombosis (PR), plaque rupture and accompanying thrombosis (TH) and volunteers, respectively, p < 0.05. The frequency of IFN-γ-producing Th17 cells was 2.33 ± 0.58%, 1.93 ± 0.2% and 2.21 ± 0.65% vs 0.38 ± 0.21% for AP, PR, TH and volunteers, p < 0.05, respectively. Furthermore, HMGB1 contributed to IFN-γ-producing Th17-cell bias by controlling expression of T-bet and RUNX3. We demonstrated, for the first time, that HMGB1 is a potential inducer of IFN-γ-producing Th17-cell bias, and that IFN-γ-producing Th17 cells might be one of the pathogenic factors in atherosclerosis.
产生干扰素-γ的Th17细胞与自身免疫性疾病有关，但其在人类中的特性仅部分为人所知。调控产生干扰素-γ的Th17细胞偏向的分子机制和外部因素尚未完全明确。本研究旨在阐明：（i）冠状动脉粥样硬化（CA）患者外周血中是否存在产生干扰素-γ的Th17细胞；（ii）循环中的高迁移率族蛋白盒（HMGB）1是否与产生干扰素-γ的Th17细胞偏向有关。
将36例经冠状动脉造影诊断为疑似或已知CA的动脉粥样硬化患者（17例女性，19例男性；年龄45 - 84岁）纳入研究队列。采集健康志愿者和患者的外周血样本，采用经典检测方法（流式细胞术、逆转录定量聚合酶链反应）检测血液成分。
我们的结果清楚地表明，不同进展期CA患者的HMGB1水平上调：仅患有动脉粥样硬化斑块（AP）的患者为5.38±1.48 ng/ml，有动脉粥样硬化斑块且部分斑块破裂但无血栓形成（PR）的患者为6.30±1.53 ng/ml，斑块破裂并伴有血栓形成（TH）的患者为5.86±1.12 ng/ml，而志愿者为1.45±0.65 ng/ml，p<0.05。产生干扰素-γ的Th17细胞频率在AP、PR、TH患者中分别为2.33±0.58%、1.93±0.2%和2.21±0.65%，志愿者为0.38±0.21%，p均<0.05。此外，HMGB1通过控制T-bet和RUNX3的表达导致产生干扰素-γ的Th17细胞偏向。我们首次证明，HMGB1是产生干扰素-γ的Th17细胞偏向的潜在诱导因子，且产生干扰素-γ的Th17细胞可能是动脉粥样硬化的致病因素之一。
