Department of Nephrology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; The First Affiliated Hospital of Jinan University, Guangzhou, People's Republic of China.
Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
Kidney Int. 2017 May;91(5):1236-1242. doi: 10.1016/j.kint.2016.12.015. Epub 2017 Feb 16.
Myeloid-derived suppressor cells (MDSCs) are recently identified immune suppressive cells in multiple chronic inflammations. Here, we investigated MDSCs in patients with end-stage renal disease (ESRD) and their clinical significance in these patients and healthy individuals (49 each). Polymorphonuclear and mononuclear MDSCs were investigated by flow cytometry. Patients with ESRD before hemodialysis presented a significantly higher level of polymorphonuclear MDSCs. Depletion of polymorphonuclear-MDSCs resolved T cell IFN-γ responses. By co-culture, T cell proliferation and the production of IFN-γ were abrogated by the addition of polymorphonuclear MDSCs in a dose-dependent manner. Both of these effects were reversed by a reactive oxygen species inhibitor. The levels of reactive oxygen species were higher in polymorphonuclear MDSCs derived from patients with ESRD than from normal individuals. The mRNA level of NOX2, the key protein complex responsible for reactive oxygen species production, was higher in ESRD-related polymorphonuclear MDSCs. The phospho-STAT3 level, a key activator of MDSCs, was higher in ESRD-related polymorphonuclear MDSCs. Finally, the polymorphonuclear MDSC level before and after hemodialysis was positively related to infectious diseases. Patients with ESRD were dichotomized into 2 groups by the amount of polymorphonuclear MDSCs. Patients with high levels of polymorphonuclear MDSCs presented with a higher incidence of infectious events. Thus, polymorphonuclear MDSCs were elevated in ESRD patients with strong immune-suppressive capability through a phospho-STAT3/reactive oxygen species pathway. Hence, polymorphonuclear MDSCs might increase the risk of infectious complications.
髓系来源的抑制细胞（MDSCs）是最近在多种慢性炎症中被鉴定出的免疫抑制细胞。在这里，我们研究了终末期肾病（ESRD）患者中的 MDSCs 及其在这些患者和健康个体中的临床意义（每组 49 人）。通过流式细胞术研究多形核和单核 MDSCs。在开始血液透析之前的 ESRD 患者中，多形核 MDSC 的水平显著升高。多形核 MDSC 的耗竭解决了 T 细胞 IFN-γ 反应。通过共培养，多形核 MDSC 以剂量依赖性方式破坏 T 细胞增殖和 IFN-γ 的产生，而这两种作用都被活性氧物质抑制剂逆转。来自 ESRD 患者的多形核 MDSC 中的活性氧物质水平高于正常个体。负责活性氧物质产生的关键蛋白复合物 NOX2 的 mRNA 水平在 ESRD 相关的多形核 MDSC 中更高。MDSC 的关键激活物 phospho-STAT3 在 ESRD 相关的多形核 MDSC 中更高。最后，血液透析前后的多形核 MDSC 水平与传染病呈正相关。根据多形核 MDSC 的量，将 ESRD 患者分为 2 组。多形核 MDSC 水平高的患者发生感染事件的几率更高。因此，通过 phospho-STAT3/活性氧物质途径，具有强免疫抑制能力的 ESRD 患者中多形核 MDSC 升高。因此，多形核 MDSC 可能会增加感染并发症的风险。
