The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells
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...
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Cell Physiol Biochem Press GmbH & Co KG
2017-12-01
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doaj-e4250aa3e43343a38aa19983867305462020-11-24T21:52:59ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-12-014451810182710.1159/000485818485818The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T CellsJunhui XiaoKunwu YuMing LiChuanyin XiongYuzhen WeiQiutang ZengBackground/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-β1 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-β. 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.https://www.karger.com/Article/FullText/485818CytokinesInflammationImmunotherapyIschaemia/reperfusion injuryRegulatory T-lymphocytes (Tregs) |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Junhui Xiao Kunwu Yu Ming Li Chuanyin Xiong Yuzhen Wei Qiutang Zeng |
spellingShingle |
Junhui Xiao Kunwu Yu Ming Li Chuanyin Xiong Yuzhen Wei Qiutang Zeng The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells Cellular Physiology and Biochemistry Cytokines Inflammation Immunotherapy Ischaemia/reperfusion injury Regulatory T-lymphocytes (Tregs) |
author_facet |
Junhui Xiao Kunwu Yu Ming Li Chuanyin Xiong Yuzhen Wei Qiutang Zeng |
author_sort |
Junhui Xiao |
title |
The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells |
title_short |
The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells |
title_full |
The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells |
title_fullStr |
The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells |
title_full_unstemmed |
The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells |
title_sort |
il-2/anti-il-2 complex attenuates cardiac ischaemia-reperfusion injury through expansion of regulatory t cells |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2017-12-01 |
description |
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-β1 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-β. 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. |
topic |
Cytokines Inflammation Immunotherapy Ischaemia/reperfusion injury Regulatory T-lymphocytes (Tregs) |
url |
https://www.karger.com/Article/FullText/485818 |
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