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在扩张型心肌病患者中,CD4 CD25 GARP调节性T细胞表现出受损的抑制功能。

CD4  CD25  GARP regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy.

作者信息

Wei Yuzhen, Yu Kunwu, Wei Hui, Su Xin, Zhu Ruirui, Shi Huairui, Sun Haitao, Luo Quan, Xu Wenbin, Xiao Junhui, Zhong Yucheng, Zeng Qiutang

机构信息

Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, TongJi Medical College, Huahzong University of Science and Technology, Wuhan, China.

The First Peoples Hospital of Tianmen City, Tianmen, China.

出版信息

Immunology. 2017 Jul;151(3):291-303. doi: 10.1111/imm.12728. Epub 2017 Mar 29.

Abstract

Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4 T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4  CD25  GARP regulatory T (Treg) cells in DCM. Forty-five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon-γ (IFN-γ), interleukin (IL-17)], and an obvious decrease in Treg number, transforming growth factor-β (TGF-β ) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4  CD25  GARP Treg cells was impaired in DCM patients upon T-cell receptor stimulation detected using CFSE dye. Lower level of TGF-β and higher levels of IFN-γ and IL-17 detected using ELISA were found in supernatants of the cultured CD4  CD25  GARP Treg cells in DCM patients compared with controls. Together, our results indicate that CD4  CD25  GARP Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients.

摘要

扩张型心肌病(DCM)是一种致命的炎症性心脏病,与免疫系统功能障碍密切相关。已证实活化的具有抑制活性的CD4 T细胞上表达的糖蛋白A重复序列占主导(GARP)。本研究旨在调查DCM患者循环中CD4 CD25 GARP调节性T(Treg)细胞的频率和功能。本研究纳入了45例DCM患者和46例对照。与对照组相比,DCM患者外周1型辅助性T细胞(Th1)和Th17数量及其相关细胞因子[干扰素-γ(IFN-γ)、白细胞介素(IL-17)]显著增加,而Treg数量、转化生长因子-β(TGF-β)水平以及叉头框P3(FOXP3)和GARP的表达明显降低。此外,使用CFSE染料检测发现,DCM患者的CD4 CD25 GARP Treg细胞在T细胞受体刺激后抑制功能受损。与对照组相比,DCM患者培养的CD4 CD25 GARP Treg细胞上清液中使用ELISA检测到的TGF-β水平较低,IFN-γ和IL-17水平较高。总之,我们的结果表明DCM患者的CD4 CD25 GARP Treg细胞存在缺陷,GARP似乎是调节表型的更好分子定义。因此,在DCM患者中更多关注GARP可能是一种有吸引力的策略。

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