The CD4(+) AT2R(+) T cell subpopulation improves post-infarction remodelling and restores cardiac function.
The CD4(+) AT2R(+) T cell subpopulation improves post-infarction remodelling and restores cardiac function.
复制标题
CD4( )AT2R( ) T 细胞亚群改善梗塞后重塑并恢复心脏功能
DOI：
10.1111/jcmm.12574
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发表时间：
2015-08
影响因子：
5.3
通讯作者：
David R
中科院分区：
文献类型：
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作者：
Skorska A;von Haehling S;Ludwig M;Lux CA;Gaebel R;Kleiner G;Klopsch C;Dong J;Curato C;Altarche-Xifró W;Slavic S;Unger T;Steinhoff G;Li J;David R
心肌梗死（MI）是导致心力衰竭（HF）的主要疾病。心肌梗死后，肾素血管紧张素系统（RAS）及其信号八肽血管紧张素II（Ang II）通过AT 1和AT 2受体（AT 1 R，AT 2 R）干扰心脏损伤/修复。我们的研究旨在破译RAS和免疫反应的细胞成分之间的联系的机制，依赖于HF的啮齿动物模型以及HF患者。流式细胞术分析显示，在大鼠心脏和脾脏中的表达增加的CD 4 + AT 2 R+细胞梗死后，但在外周血中的减少。在HF患者中也观察到后者。大鼠循环血、梗死后心脏和脾脏中的CD 4 + AT 2 R + T细胞分别占CD 4+细胞的3.8 ± 0.4%、23.2 ± 2.7%和22.6 ± 2.6%。血液中CD 4 + T细胞中的CD 4 + AT 2 R + T细胞从健康对照的2.6 ± 0.2%降低至患者的1.7 ± 0.4%。此外，我们还鉴定了表达调节性FoxP 3、分泌白细胞介素-10和其他炎症相关细胞因子的CD 4 + AT 2 R + T细胞。此外，心肌内注射MI诱导的脾CD 4 + AT 2 R + T细胞到MI受体大鼠导致梗死面积减少和心脏性能改善。我们将CD 4 + AT 2 R+细胞定义为改善MI后心脏功能的T细胞亚群，其与大鼠MI模型中梗死面积减小相对应。我们的研究结果表明，CD 4 + AT 2 R+细胞作为一个有前途的人口再生治疗，通过心肌移植，药理学AT 2 R激活或其组合。
Myocardial infarction (MI) is a major condition causing heart failure (HF). After MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular components of the immune response relying on a rodent model of HF as well as HF patients. Flow cytometric analyses showed an increase in the expression of CD4+ AT2R+ cells in the rat heart and spleen post-infarction, but a reduction in the peripheral blood. The latter was also observed in HF patients. The frequency of rat CD4+ AT2R+ T cells in circulating blood, post-infarcted heart and spleen represented 3.8 ± 0.4%, 23.2 ± 2.7% and 22.6 ± 2.6% of the CD4+ cells. CD4+ AT2R+ T cells within blood CD4+ T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD4+ AT2R+ T cells which expressed regulatory FoxP3, secreted interleukin-10 and other inflammatory-related cytokines. Furthermore, intramyocardial injection of MI-induced splenic CD4+ AT2R+ T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD4+ AT2R+ cells as a T cell subset improving heart function post-MI corresponding with reduced infarction size in a rat MI-model. Our results indicate CD4+ AT2R+ cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.