The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells
The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells
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DOI：
10.1159/000485818
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Zeng, Qiutang
中科院分区：
文献类型：
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作者：
Xiao, Junhui;Yu, Kunwu;Zeng, Qiutang
背景/目标：调节性T细胞（Regulatory T cells，Tcells）可抑制心肌缺血/再灌注损伤（myocardial ischaemia/reperfusion injury，MIRI）的免疫损伤，但其分离和体外扩增应用于临床仍面临挑战。在这里，我们研究了IL-2/抗IL-2复合物（IL-2C），调节性T细胞扩增的介质，是否可以减弱小鼠MIRI。研究方法：在8-10周龄的雄性C57 BL/6小鼠中手术诱导心肌I/R，所述小鼠被随机分配到1）假手术组（Sham），2）磷酸盐缓冲盐水（PBS），3）IL-2-抗-IL-2 Ab复合物（IL-2C），或4）假手术组，5）PBS，6）MIRI后的IL-2C，或7）IL-2C，8）IL-2C+抗-CD 25 mAb，或9）IL-2C; 10）IL-2C+抗TGF-β 1 mAb，11）IL-2C+抗IL-10 mAb。在不同的时间点测量以下参数：梗死面积、心肌细胞凋亡、脾细胞、TGFAP的抑制功能和炎性因子的存在。此外，进行免疫组织化学分析。结果：观察到MIRI可激活T细胞。在MIRI前给予IL-2C可诱导脾和心脏Treg扩增，减少Th 1和Th 17细胞数量，改善心肌功能，并减少MIRI后炎性细胞浸润和凋亡。此外，IL-2C给药减少了心脏中炎性细胞因子的表达，并减弱了脾细胞的增殖。用抗-CD 25 mAb消耗Tcl 3消除了IL-2C的有益作用。然而，IL-2C介导的心肌保护不依赖于IL-10或TGF-β。此外，MIRI后给予IL-2C并没有减少梗死面积，但确实轻微改善了心肌功能并减少了心肌纤维化。结论：我们的研究结果表明，IL-2C诱导的Treg扩增在体内减弱MIRI并改善心肌恢复，表明IL-2C是心肌IRI的有希望的治疗靶点。(C)2017作者由S.发布Karger AG，巴塞尔
Background/Aims: Regulatory T cells (Tregs) can suppress immunologic damage in myocardial ischaemia/reperfusion injury (MIRI), however, the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate MIRI in mice. Methods: Myocardial I/R was surgically induced in male C57BL/6 mice, aged 8-10 weeks, that were randomly assigned to 1) sham group (Sham), 2) Phosphate Buffered Saline (PBS), 3) IL-2-anti-IL-2 Ab complex (IL-2C), or 4) sham group, 5) PBS, 6) IL-2C after MIRI, or 7) IL-2C, 8) IL-2C+anti-CD25 mAbs, or 9) IL-2C; 10) IL-2C+anti-TGF-b1 mAbs, 11) IL-2C+anti-IL-10 mAbs. The following parameters were measured at different time points: infarct area, myocardial apoptosis, splenocytes, the inhibitory function of Tregs, and presence of inflammatory factors. In addition, immunohistochemistry analysis was performed. Results: We observed that Tregs were activated in response to MIRI. IL-2C administered before MIRI induced Treg expansion in both spleen and heart, attenuated Th1 and Th17 cell numbers, improved myocardial function, and attenuated both infiltration of inflammatory cells and apoptosis after MIRI. Furthermore, IL-2C administration reduced expression of inflammatory cytokines in the heart and attenuated proliferation of splenic cells. Depletion of Tregs with anti-CD25 mAb abrogated the beneficial effects of IL-2C. However, IL-2C-mediated myocardial protection was not dependent on either IL-10 or TGF-beta. In addition, IL-2C administration after MIRI did not reduce infarct area, but did improve myocardial function slightly and reduced myocardial fibrosis. Conclusion: Our results demonstrate that IL-2C-induced Treg expansion attenuates MIRI and improves myocardial recovery in vivo, suggesting that IL-2C is a promising therapeutic target for myocardial IRI. (C) 2017 The Author(s) Published by S. Karger AG, Basel