Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Experimental, Diagnostic, Specialty Medicine, Nephrology, Dialysis, and Renal Transplant Unit, S. Orsola University Hospital, Bologna, Italy.
Am J Transplant. 2019 Sep;19(9):2407-2414. doi: 10.1111/ajt.15369. Epub 2019 Apr 25.
Erythropoietin (EPO) is a glycoprotein produced mainly by the adult kidney in response to hypoxia and is the crucial regulator of red blood cell production. EPO receptors (EPORs), however, are not confined to erythroid cells, but are expressed by many organs including the heart, brain, retina, pancreas, and kidney, where they mediate EPO-induced, erythropoiesis-independent, tissue-protective effects. Some of these tissues also produce and locally release small amounts of EPO in response to organ injury as a mechanism of self-repair. Growing evidence shows that EPO possesses also important immune-modulating effects. Monocytes can produce EPO, and autocrine EPO/EPOR signaling in these cells is crucial in maintaining immunologic self-tolerance. New data in mice and humans also indicate that EPO has a direct inhibitory effect on effector/memory T cells, while it promotes formation of regulatory T cells. This review examines the nonerythropoietic effects of EPO, with a special emphasis on its modulating activity on innate immune cells and T cells and on how it affects transplant outcomes.
促红细胞生成素（EPO）是一种主要由成人肾脏产生的糖蛋白，对缺氧有反应，是红细胞生成的关键调节剂。然而，EPO 受体（EPORs）不仅局限于红细胞，而且在许多器官中表达，包括心脏、大脑、视网膜、胰腺和肾脏，在这些器官中，它们介导 EPO 诱导的、与红细胞生成无关的组织保护作用。其中一些组织也会在器官损伤时产生和局部释放少量的 EPO，作为自我修复的一种机制。越来越多的证据表明，EPO 还具有重要的免疫调节作用。单核细胞可以产生 EPO，这些细胞中的自分泌 EPO/EPOR 信号对于维持免疫自身耐受至关重要。小鼠和人类的新数据还表明，EPO 对效应/记忆 T 细胞具有直接抑制作用，同时促进调节性 T 细胞的形成。这篇综述探讨了 EPO 的非红细胞生成作用，特别强调了它对固有免疫细胞和 T 细胞的调节活性，以及它如何影响移植结果。
