Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149, Trieste, Italy.
Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy and Center for Translational Cardiology, Azienda Sanitaria Universitaria Integrata di Trieste, 34129, Trieste, Italy.
Nat Commun. 2018 Jun 26;9(1):2432. doi: 10.1038/s41467-018-04908-z.
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, Tnfsf11, 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.
心肌细胞的增殖在出生时停止，此时心脏不再接触母体血液，同样也不再接触调节性 T 细胞（Tregs），因为 Tregs 会被扩增以促进母体对胎儿的耐受性。在这里，我们报告了 Tregs 在促进心肌细胞增殖中的作用。Treg 条件培养基促进心肌细胞增殖，类似于来自妊娠动物的血清。在怀孕母亲的心脏中检测到增殖性心肌细胞，而在怀孕期间耗尽 Treg 会减少母体和胎儿心肌细胞的增殖。心肌梗死后耗尽 Treg 会导致心脏功能下降、大量炎症和胶原沉积稀少。相比之下，Treg 注射会减少梗死面积、保持收缩性并增加增殖性心肌细胞的数量。Treg 分泌的六种因子（Cst7、Tnfsf11、Il33、Fgl2、Matn2 和 Igf2）的过表达可复制治疗效果。总之，Tregs 以旁分泌的方式促进胎儿和母体心肌细胞的增殖，并改善心肌梗死的预后。
