IFN-γ-producing Th17 cells bias by HMGB1-T-bet/RUNX3 axis might contribute to progression of coronary artery atherosclerosis
IFN-γ-producing Th17 cells bias by HMGB1-T-bet/RUNX3 axis might contribute to progression of coronary artery atherosclerosis
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HMGB1-T-bet/RUNX3 轴产生 IFN-γ 的 Th17 细胞偏向可能导致冠状动脉粥样硬化的进展
DOI：
10.1016/j.atherosclerosis.2015.09.037
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发表时间：
2015-12-01
期刊：
影响因子：
5.3
通讯作者：
Xu, Huaxi
中科院分区：
文献类型：
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作者：
Su, Zhaoliang;Lu, Hongxiang;Xu, Huaxi
背景：产生ifn - 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。控制ifn - γ产生的th17细胞偏倚的分子机制和外部因素尚不完全清楚。目前的工作是澄清是否(i)产生ifn - γ的Th17细胞存在于冠状动脉粥样硬化（CA）患者的外周循环中；（ii）循环中的高迁移率群盒（HMGB） 1与产生ifn - γ的th17细胞偏倚有关。方法：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（女性17例，男性19例，年龄45-84岁）纳入研究队列。采集健康志愿者和患者外周血样本，采用流式细胞术、RT-qPCR等经典检测方法测定血液成分。结果与结论：我们的研究结果清楚地表明，HMGB1在不同进展性CA患者中上调：仅动脉粥样硬化斑块（AP）、动脉粥样硬化斑块及部分斑块破裂、无血栓形成（PR）、斑块破裂伴血栓形成（TH）和志愿者中分别上调5.38 +/- 1.48 ng/ml、6.30 +/- 1.53 ng/ml和5.86 +/- 1.12 ng/ml和1.45 +/- 0.65 ng/ml, p < 0.05。产生ifn - γ的Th17细胞的频率分别为2.33 +/- 0.58%、1.93 +/- 0.2%和2.21 +/- 0.65%，AP、PR、TH和志愿者分别为0.38 +/- 0.21%,p < 0.05。此外，HMGB1通过控制T-bet和RUNX3的表达，促进了ifn - γ产生的th17细胞偏倚。我们首次证明HMGB1是产生ifn -g的Th17细胞偏向的潜在诱导剂，并且产生ifn - γ的Th17细胞可能是动脉粥样硬化的致病因素之一。2015爱思唯尔爱尔兰有限公司版权所有。
Background: IFN-gamma-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-gamma-producing Th17-cell bias are incompletely understood. The present work was to clarify whether (i) IFN-gamma-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-gamma-producing Th17-cell bias.Methods: 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.Results and conclusion: 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-gamma-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-gamma-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-g-producing Th17-cell bias, and that IFN-gamma-producing Th17 cells might be one of the pathogenic factors in atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.