Interleukin-37 and Dendritic Cells Treated With Interleukin-37 Plus Troponin I Ameliorate Cardiac Remodeling After Myocardial Infarction.
Interleukin-37 and Dendritic Cells Treated With Interleukin-37 Plus Troponin I Ameliorate Cardiac Remodeling After Myocardial Infarction.
复制标题
白细胞介素 - 37以及用白细胞介素 - 37加肌钙蛋白I处理的树突状细胞可改善心肌梗死后的心脏重构。
DOI：
10.1161/jaha.116.004406
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发表时间：
2016-12-05
影响因子：
5.4
通讯作者：
Zeng Q
中科院分区：
文献类型：
--
作者：
Zhu R;Sun H;Yu K;Zhong Y;Shi H;Wei Y;Su X;Xu W;Luo Q;Zhang F;Zhu Z;Meng K;Zhao X;Liu Y;Mao Y;Cheng P;Mao X;Zeng Q
过度的免疫介导的炎症反应在梗死后心室重构中起有害作用。白细胞介素-37（IL-37）是先天性免疫和适应性免疫的抑制剂。然而，IL-37和IL-37加肌钙蛋白I（TnI）处理的树突状细胞（DC）在心肌梗死（MI）后心室重塑中的确切作用仍然难以捉摸。 通过永久性结扎左前降支动脉诱导MI。我们的结果表明，重组人IL-37治疗可显着改善MI后的心室重塑，表现为梗死面积缩小、心脏功能改善、死亡率降低、炎症反应限制、心肌纤维化减少和心肌细胞凋亡抑制。在体外，我们检查了雄性C57 BL/6小鼠的IL-37加TnI条件DC的表型及其影响调节性T细胞数量的能力。我们的研究结果表明，IL-37加TnI处理的DC获得了致耐受性DC（tDC）的特征，并在与脾CD 4 + T细胞共培养时扩增了调节性T细胞的数量。有趣的是，我们还发现过继转移这些负载抗原的tDC显著增加了脾脏中调节性T细胞的数量，减弱了梗死心脏中炎性细胞的浸润，减少了心肌纤维化，并改善了心脏功能。我们的研究结果揭示了IL-37或IL-37加TnI处理的tDC在MI后重塑中的有益作用，这可能是通过重建致耐受性免疫应答介导的，表明IL-37或IL-37加TnI处理的tDC的过继转移可能是MI后心室重塑的新治疗策略。
Excessive immune‐mediated inflammatory reactions play a deleterious role in postinfarction ventricular remodeling. Interleukin‐37 (IL‐37) emerges as an inhibitor of both innate and adaptive immunity. However, the exact role of IL‐37 and IL‐37 plus troponin I (TnI)–treated dendritic cells (DCs) in ventricular remodeling after myocardial infarction (MI) remains elusive. MI was induced by permanent ligation of the left anterior descending artery. Our results showed that treatment with recombinant human IL‐37 significantly ameliorated ventricular remodeling after MI, as demonstrated by decreased infarct size, better cardiac function, lower mortality, restricted inflammatory responses, decreased myocardial fibrosis, and inhibited cardiomyocyte apoptosis. In vitro, we examined the phenotype of IL‐37 plus TnI–conditioned DCs of male C57BL/6 mice and their capacity to influence the number of regulatory T cells. Our results revealed that IL‐37 plus TnI–conditioned DCs obtained the characteristics of tolerogenic DCs (tDCs) and expanded the number of regulatory T cells when co‐cultured with splenic CD4+ T cells. Interestingly, we also found that adoptive transfer of these antigen‐loaded tDCs markedly increased the number of regulatory T cells in the spleen, attenuated the infiltration of inflammatory cells in the infarct hearts, decreased myocardial fibrosis, and improved cardiac function. Our results reveal a beneficial role of IL‐37 or tDCs treated with IL‐37 plus TnI in post‐MI remodeling that is possibly mediated by reestablishing a tolerogenic immune response, indicating that IL‐37 or adoptive transfer of IL‐37 plus TnI–treated tDCs may be a novel therapeutic strategy for ventricular remodeling after MI.