mTOR inhibitor rapamycin induce polymorphonuclear myeloid-derived suppressor cells mobilization and function in protecting against acute graft-versus-host disease after bone marrow transplantation
mTOR inhibitor rapamycin induce polymorphonuclear myeloid-derived suppressor cells mobilization and function in protecting against acute graft-versus-host disease after bone marrow transplantation
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mTOR 抑制剂雷帕霉素诱导多形核骨髓源性抑制细胞动员并在骨髓移植后预防急性移植物抗宿主病中发挥作用
DOI：
10.1016/j.clim.2017.11.005
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发表时间：
2018-02-01
影响因子：
8.6
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Lin, Yu;Wang, Binsheng;Huang, He
哺乳动物靶向雷帕霉素(MTOR)抑制剂雷帕霉素(RapA)已被证明是治疗骨髓移植后急性移植物抗宿主病(AGVHD)的有效免疫抑制剂。髓系来源的抑制细胞(MDSCs)在aGVHD调节中也有保护作用。然而，在aGVHD模型中，RAPA和MDSCs之间的关系尚不清楚。同时，RAPA对MDSCs不同亚群的影响也没有得到很好的描述。在这项研究中，我们证明了在aGVHD小鼠模型中，RAPA的体内给药导致了多形核多形核干细胞(PMN-MDSCs)的扩增和功能增强。RAPA可通过上调精氨酸酶1(Arg1)和诱导型一氧化氮合酶(INOS)的表达增强PMN-MDSCs的抑制功能。此外，RAPA对体外培养的小鼠骨髓来源的PMN-MDSCs也有较强的免疫抑制作用，而对单核细胞MDSCs(M-MDSCs)则相反。我们在体外研究中发现，经RAPA处理的PMN-MDSCs能够抑制Th1/Th2细胞的分化，促进调节性T细胞的诱导。(C)2017 Elsevier Inc.保留所有权利。
The mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) has been shown to be an effective immunosuppressor in the management of acute graft-versus-host disease (aGVHD) after bone marrow transplantation. Myeloid-derived suppressor cells (MDSCs) also have a protective effect in aGVHD regulation. However, the relationship between RAPA and MDSCs in aGVHD models is unclear. Meanwhile, the effect of RAPA on different subgroups of MDSCs is also less well described. In this study, we demonstrate that in vivo administration of RAPA results in the expansion and functional enhancement of polymorphonuclear MDSCs (PMN-MDSCs) in a murine model of aGVHD. RAPA treatment can enhance the suppressive function of PMN-MDSCs via up-regulation of arginase1 (Arg1) and induced nitric oxide synthase (iNOS) at later time points. Moreover, RAPA can also induce a strong immunosuppressive function in PMN-MDSCs from murine bone marrow in vitro, but has a contrary effect on monocytic MDSCs (M-MDSCs). We found that RAPA-treated PMN-MDSCs can restrain the differentiation of Th1/Th2 cells and promote induction of regulatory T cells in in vitro studies. (C) 2017 Elsevier Inc. All rights reserved.