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.

雷帕霉素（mTOR）抑制剂雷帕霉素（RAPA）的哺乳动物靶点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。骨髓来源的抑制细胞（MDSC）在aGVHD调节中也具有保护作用。但是，在aGVHD模型中RAPA与MDSC之间的关系尚不清楚。同时，RAPA对MDSCs不同亚组的作用也没有得到很好的描述。在这项研究中，我们证明在aGVHD鼠模型中，体内RAPA给药可导致多形核MDSC（PMN-MDSC）的扩增和功能增强。RAPA处理可通过以下途径增强PMN-MDSC的抑制功能在稍后的时间点上调精氨酸酶1（Arg1）和诱导型一氧化氮合酶（iNOS）。此外，RAPA还可以在体外从鼠骨髓中诱导PMN-MDSCs的强免疫抑制功能，但对单核MDSCs（M-MDSCs）具有相反的作用。我们发现，在体外研究中，RAPA处理的PMN-MDSCs可以抑制Th1 / Th2细胞的分化并促进诱导调节性T细胞。