CD4(+)CD25(+)GARP(+) regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy
CD4(+)CD25(+)GARP(+) regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy
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CD4( )CD25( )GARP( ) 调节性 T 细胞在扩张型心肌病患者中表现出抑制功能受损
DOI：
10.1111/imm.12728
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发表时间：
2017
期刊：
影响因子：
6.4
通讯作者：
Zeng Qiutang
中科院分区：
文献类型：
--
作者：
Wei Yuzhen;Yu Kunwu;Wei Hui;Su Xin;Zhu Ruirui;Shi Huairui;Sun Haitao;Luo Quan;Xu Wenbin;Xiao Junhui;Zhong Yucheng;Zeng Qiutang
扩张型心肌病（Dilated cardiomyopathy，DCM）是一种致死性的炎症性心脏病，与免疫系统功能紊乱密切相关。已经建立了在具有抑制活性的活化的CD 4 +T细胞上表达的糖蛋白A重复优势（GARP）。本研究旨在探讨DCM患者外周血中CD 4 + CD 25 +GARP+调节性T（Treg）细胞的频率和功能。本研究入组了45例DCM患者和46例对照。与对照组相比，DCM患者外周血Th 1、Th 17细胞数量及其相关细胞因子γ干扰素（IFN-γ）、白细胞介素（IL-17）显著增加，Treg细胞数量、转化生长因子β1（TGF-β1）水平、叉头盒P3（FOXP 3）和GARP表达显著降低。此外，在使用CFSE染料检测到T细胞受体刺激后，DCM患者中CD 4 + CD 25 +GARP+Treg细胞的抑制功能受损。DCM患者CD 4 + CD 25 +GARP+Treg细胞培养上清中TGF-β 1水平低于对照组，IFN-γ和IL-17水平高于对照组。总之，我们的结果表明，CD 4 + CD 25 +GARP+Treg细胞在DCM患者中是有缺陷的，GARP似乎是调节表型的更好的分子定义。因此，重视扩张型心肌病患者的GARP可能是一个有吸引力的策略。
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‐β1(TGF‐β1) 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‐β1and higher levels of IFN‐γand 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.