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动脉粥样硬化性脑梗死患者外周血Th17/Treg失衡

Peripheral Th17/Treg imbalance in patients with atherosclerotic cerebral infarction.

作者信息

Li Qing, Wang Yiping, Yu Feng, Wang Yuan Min, Zhang Cuiping, Hu Chaojie, Wu Zhiwei, Xu Xiucai, Hu Shilian

机构信息

The Central Laboratory of Medical Research Center, Anhui Provincial Hospital Hefei, Anhui 230001, PR China.

出版信息

Int J Clin Exp Pathol. 2013 May 15;6(6):1015-27. Print 2013.

Abstract

OBJECTIVE

CD4(+)CD25(+) regulatory T (Treg) cells and Th17 cells play important roles in peripheral immunity. Oxidized low-density lipoprotein (ox-LDL) is an instrumental factor in atherogenesis. However, the changes of Th17/Treg cells in patients with acute cerebral Infarction (ACI) and impact on Th17/Treg by ox-LDL are not clear. Here, we examined the balance of Th17/Treg in ACI patients and the effect of ox-LDL on this balance.

MATERIALS AND METHODS

The frequencies of Th17 and Treg cells, key transcription factors and relevant cytokines were examined in patients with ACI, Transient ischemic attack (TIA) and controls. The correlations of cytokines, inflammatory biomarkers and ox-LDL in serum to Th17/Treg frequency, and the effects of ox-LDL on Th17/Treg cells in vitro were analyzed.

RESULTS

ACI patients have shown a significant increase of Th17 frequency, RORγt expression and Th17 related cytokines (IL-17 and IL-6 ) levels, and a clear decline of Treg frequency, Foxp3 expression, suppressive function and regulatory cytokines (IL-10 and TGF-β1) levels. Furthermore, TIA patients also have notable variation as compared to control group. Serum ox-LDL and inflammatory biomarkers were positively correlated with the frequency of Th17 cells and negatively correlated with the frequency of Treg cells. Treg and Th17 cells from ACI patients were significantly susceptible to ox-LDL-mediated alterations in vitro.

CONCLUSIONS

Th17/Treg cells were imbalanced in ACI patients, and ox-LDL may contribute to this imbalance and lead to the occurrence of ACI suggesting their pathogenetic role in ACI.

摘要

目的

CD4(+)CD25(+)调节性T(Treg)细胞和Th17细胞在外周免疫中发挥重要作用。氧化型低密度脂蛋白(ox-LDL)是动脉粥样硬化形成的一个重要因素。然而,急性脑梗死(ACI)患者中Th17/Treg细胞的变化以及ox-LDL对Th17/Treg的影响尚不清楚。在此,我们研究了ACI患者中Th17/Treg的平衡以及ox-LDL对这种平衡的影响。

材料与方法

检测了ACI患者、短暂性脑缺血发作(TIA)患者及对照组中Th17和Treg细胞的频率、关键转录因子及相关细胞因子。分析了血清中细胞因子、炎症生物标志物和ox-LDL与Th17/Treg频率的相关性,以及ox-LDL体外对Th17/Treg细胞的影响。

结果

ACI患者Th17频率、RORγt表达及Th17相关细胞因子(IL-17和IL-6)水平显著升高,Treg频率、Foxp3表达、抑制功能及调节性细胞因子(IL-10和TGF-β1)水平明显下降。此外,与对照组相比,TIA患者也有显著变化。血清ox-LDL和炎症生物标志物与Th17细胞频率呈正相关,与Treg细胞频率呈负相关。体外实验中,来自ACI患者的Treg和Th17细胞对ox-LDL介导的改变显著敏感。

结论

ACI患者中Th17/Treg细胞失衡,ox-LDL可能导致这种失衡并促使ACI的发生,提示它们在ACI发病机制中的作用。

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