Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction

被引:141
作者
Zacchigna, Serena [1 ,2 ,3 ]
Martinelli, Valentina [4 ]
Moimas, Silvia [2 ,3 ,4 ]
Colliva, Andrea [1 ]
Anzini, Marco [2 ,3 ]
Nordio, Andrea [2 ,3 ]
Costa, Alessia [1 ]
Rehman, Michael [1 ]
Vodret, Simone [1 ]
Pierro, Cristina [1 ]
Colussi, Giulia [4 ]
Zentilin, Lorena [4 ]
Gutierrez, Maria Ines [4 ]
Dirkx, Ellen [4 ]
Long, Carlin [4 ]
Sinagra, Gianfranco [2 ,3 ]
Klatzmann, David [5 ,6 ]
Giacca, Mauro [2 ,3 ,4 ]
机构
[1] Int Ctr Genet Engn & Biotechnol, Cardiovasc Biol Lab, I-34149 Trieste, Italy
[2] Univ Trieste, Dept Med Surg & Hlth Sci, I-34127 Trieste, Italy
[3] Azienda Sanit Univ Integrata Trieste, Ctr Translat Cardiol, I-34129 Trieste, Italy
[4] Int Ctr Genet Engn & Biotechnol, Mol Med Lab, I-34149 Trieste, Italy
[5] UPMC Univ Paris 06, Sorbonne Univ, UMR S 959, INSERM,Immunol Immunopathol Immunotherapy, F-75005 Paris, France
[6] Grp Hosp Pitie Salpetriere, AP HP, Dept Biotherapies, Clin Invest Ctr Biotherapy & Inflammat Immunopath, F-75013 Paris, France
来源
NATURE COMMUNICATIONS | 2018年 / 9卷
基金
欧洲研究理事会;
关键词
PERIPHERAL-BLOOD; MOUSE MODEL; GROWTH; CANCER; INTERLEUKIN-33; ACCUMULATION; REGENERATION; METASTASIS; DISEASE; LYMPHOCYTES;
D O I
10.1038/s41467-018-04908-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infarction results in depressed cardiac function, massive inflammation, and scarce collagen deposition. In contrast, Treg injection reduces infarct size, preserves contractility, and increases the number of proliferating cardiomyocytes. The overexpression of six factors secreted by Tregs (Cst7, Tnfsfll, Il33, Fgl2, Matn2, and Igf2) reproduces the therapeutic effect. In conclusion, Tregs promote fetal and maternal cardiomyocyte proliferation in a paracrine manner and improve the outcome of myocardial infarction.
引用
收藏
页数:12
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