NK Cell Regulatory Property is Involved in the Protective Role of MSC-Derived Extracellular Vesicles in Renal Ischemic Reperfusion Injury
NK Cell Regulatory Property is Involved in the Protective Role of MSC-Derived Extracellular Vesicles in Renal Ischemic Reperfusion Injury
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NK 细胞调节特性参与 MSC 衍生的细胞外囊泡在肾缺血再灌注损伤中的保护作用
DOI：
10.1089/hum.2016.057
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发表时间：
2016
影响因子：
4.2
通讯作者：
Zhu Yingjian
中科院分区：
文献类型：
--
作者：
Zou Xiangyu;Gu Di;Zhang Guangyuan;Zhong Liang;Cheng Zhongliang;Liu Guohua;Zhu Yingjian
免疫调节作用被认为是间充质基质细胞来源的细胞外囊泡（MSC-EVs）治疗肾缺血再灌注损伤（IRI）的一个重要方面，但其具体机制尚不清楚。本研究旨在通过靶向自然杀伤细胞（NK细胞）来检测人MSC-EV对肾脏IRI的作用并探讨其可能的机制。数据表明，EV减少脾和缺血肾中的NK细胞。EVs和抗体依赖性NK细胞耗竭在IRI大鼠中显示出保护作用。建立脾切除模型，探讨脾在这一过程中的作用。这表明，在没有脾脏的情况下，EV仍然具有NK细胞调节能力和肾脏保护作用，这与先前发表的MSC特性不同。此外，还观察到在损伤的肾脏中的趋化因子的下调和RNA通过EV在体外的递送。通过microRNA芯片检测，发现MSC-EVs与成纤维细胞EVs相比，多种炎症相关microRNA表达量较高。因此，这些结果表明，MSC-EVs可以通过减少NK细胞来改善肾脏缺血再灌注损伤，而脾脏在这个过程中不是必需的。另一个因素是损伤肾组织中趋化因子的调节，可能涉及MSC-EVs中各种microRNA的转移。这为未来的临床应用提供了方向。
Immunomodulation has been regarded as an important therapeutic aspect of mesenchymal stromal cell–derived extracellular vesicles (MSC-EVs) in renal ischemic reperfusion injury (IRI), and the specific mechanism still unclear. Here, we attempt to test the function of human MSC-EVs on renal IRI by targeting the natural killer (NK) cells and to investigate the possible mechanism. Data indicated that EVs decreased NK cells in spleen and ischemic kidney. Both the EVs and antibody-dependent depletion of NK cells displayed a protective role in IRI rats. Moreover, the splenectomy model was established to evaluate the role of spleen in this process. It showed that the NK cell regulatory ability and renal protective effects by EVs still exist without spleen, which is unlike MSC properties published previously. Further, the down-regulation of chemokines in injured kidney and the delivery of RNAs through EVsin vitrowere also observed. Through the microRNA array test, various inflammation-related microRNAs highly expressed in MSC-EVs compared with fibroblast EVs were tested. Thus, these results indicated that MSC-EVs could ameliorate renal ischemic reperfusion injury by decreasing NK cells and the spleen is not necessary in this process. The regulation of chemokines in injured kidney was the other factor, and the transfer of various microRNAs in the MSC-EVs may be involved. This provides direction for future clinical applications.