Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
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调节性 T 细胞的过继转移可预防柯萨奇病毒 B3 诱导的心脏纤维化
DOI：
10.1371/journal.pone.0074955
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Xiong S
中科院分区：
文献类型：
--
作者：
Cao Y;Xu W;Xiong S
研究背景病毒性心肌炎晚期心肌纤维化导致收缩功能障碍和心室扩张，是心肌炎发展为扩张型心肌病（dilated cardiomyopathy，DCM）和充血性心力衰竭（congestive heart failure，HF）等严重心血管疾病的主要致病因素。最近的研究表明，调节性T细胞（Tcells）参与肝纤维化和肺纤维化的纤维化过程。然而，TdR在病毒性心肌炎引起的心脏纤维化的发展中的作用及其治疗潜力仍不清楚。方法/主要结果腹腔注射柯萨奇病毒B3（Coxsackievirus B3，CVB 3）诱导BALB/c小鼠心肌纤维化，采用天狼猩红染色，检测I型胶原、基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶-3（MMP-3）和金属蛋白酶组织抑制剂-1（TIMP-1）的表达水平。在病毒性心肌炎过程中，心肌Treg频率下调，且与心肌纤维化程度呈负相关，为探讨Treg在CVB诱导的心肌纤维化中的作用，通过体内注射抗CD 25单克隆抗体耗竭Treg，导致心肌纤维化加重。与此一致的是，将分离的Treg过继转移到小鼠体内后，证实CVB 3诱导的心脏纤维化显着改善。采用白细胞介素-10（IL-10）中和抗体在体内和体外研究Treg治疗作用的分子机制。结果发现，在Treg转移后施用抗IL-10 mAb消除了Treg的治疗效果，并且Treg对心脏成纤维细胞胶原产生的抑制主要通过IL-10介导。结论TCFs通过分泌IL-10对CVB 3诱导的心肌纤维化具有保护作用，为今后治疗心肌纤维化提供了一种新的选择。
Background Cardiac fibrogenesis in the late stage of viral myocarditis causing contractile dysfunction and ventricular dilatation, is a major pathogenic factor for the progression of myocarditis to serious cardiovascular diseases including dilated cardiomyopathy (DCM) and congestive heart failure (HF). Recent studies indicate that regulatory T cells (Tregs) are involved in the fibrotic process of liver and lung fibosis. However, the role of Tregs in the development of viral myocarditis-caused cardiac fibrosis and their therapeutic potential remains unclear. Methodology/Principal Findings Myocardial fibrosis was induced in BALB/c mice by intraperitoneal injection of Coxsackievirus B3 (CVB3) assessed by picrosirius red staining and detection of expression levels of collagen I, matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Myocardial Treg frequency was down-regulated during the course of viral myocarditis and a negative correlation with the severity of cardiac fibrosis was found. To explore the role of Tregs in CVB-induced cardiac fibrosis, Treg was in vivo depleted by injecting anti-CD25 mAb which resulted in aggravation of cardiac fibrosis. In consistent with that, after adoptive transfer of isolated Tregs into mice, significant amelioration of CVB3-induced cardiac fibrosis was confirmed. Interleukin-10 (IL-10) neutralizing antibodies were used in vivo and in vitro to explore the molecular mechanism of the therapeutic effect of Treg. It was found that administration of anti-IL-10 mAb after Treg transfer abrogated Treg’s treating effect and the inhibition of Treg on collagen production by cardiac fibroblasts was mediated mainly through IL-10. Conclusion/Significance Our data suggested that Tregs have a protective role in the fibrotic process of CVB3-induced cardiac fibrosis via secreting IL-10 and might provide an alternative option for the future treatment of cardiac fibrosis.
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影响因子：
3.7
作者：
Liu F;Liu J;Weng D;Chen Y;Song L;He Q;Chen J
通讯作者：
Chen J
影响因子：
37.8
作者：
Verma SK;Krishnamurthy P;Barefield D;Singh N;Gupta R;Lambers E;Thal M;Mackie A;Hoxha E;Ramirez V;Qin G;Sadayappan S;Ghosh AK;Kishore R
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Kishore R
影响因子：
24
作者：
Assomull, Ravi G.;Prasad, Sanjay K.;Pennell, Dudley J.
通讯作者：
Pennell, Dudley J.
白介素10在抑制肠炎的调节T细胞功能中的重要作用。
影响因子：
15.3
作者：
Asseman, C;Mauze, S;Leach, M W;Coffman, R L;Powrie, F
通讯作者：
Powrie, F
影响因子：
19.6
作者：
Tapmeier, Thomas T.;Fearn, Amy;Wong, Wilson
通讯作者：
Wong, Wilson