Expansion of polymorphonuclear myeloid-derived suppressor cells in patients with end-stage renal disease may lead to infectious complications
Expansion of polymorphonuclear myeloid-derived suppressor cells in patients with end-stage renal disease may lead to infectious complications
复制标题
终末期肾病患者中多形核骨髓源性抑制细胞的扩增可能导致感染性并发症。
DOI：
10.1016/j.kint.2016.12.015
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发表时间：
2017-05-01
影响因子：
19.6
通讯作者：
Li, Xing
中科院分区：
文献类型：
--
作者：
Xing, Yan-Fang;Cai, Rui-Ming;Li, Xing
髓源性抑制细胞（MDSC）是近年来发现的在多种慢性炎症中的免疫抑制细胞。在这里，我们研究了终末期肾病（ESRD）患者的MDSC及其在这些患者和健康个体（各49例）中的临床意义。通过流式细胞术研究多态性和单核MDSC。血液透析前ESRD患者的多形MDSC水平显著较高。多形核-MDSC的消耗解决了T细胞IFN-γ应答。通过共培养，T细胞增殖和IFN-γ的产生通过以剂量依赖性方式添加多形MDSC而消除。这两种效应都被活性氧抑制剂逆转。来自ESRD患者的多形核MDSC中活性氧水平高于来自正常个体的活性氧水平。在ESRD相关的多形核MDSC中，负责活性氧产生的关键蛋白复合物NOX 2的mRNA水平较高。磷酸化STAT 3水平是MDSC的关键激活因子，在ESRD相关的多形核MDSC中更高。血液透析前后多形核MDSC水平与感染性疾病呈正相关。根据多形核MDSC的数量将ESRD患者分为2组。具有高水平的多形MDSC的患者呈现出较高的感染事件发生率。因此，在具有强免疫抑制能力的ESRD患者中，通过磷酸化-STAT 3/活性氧途径，多形核MDSC升高。因此，多形MDSC可能会增加感染并发症的风险。
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-gamma responses. By co-culture, T cell proliferation and the production of IFN-gamma 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.