PMID- 29132870 OWN - NLM STAT- MEDLINE DCOM- 20190318 LR - 20190318 IS - 1521-7035 (Electronic) IS - 1521-6616 (Linking) VI - 187 DP - 2018 Feb TI - mTOR inhibitor rapamycin induce polymorphonuclear myeloid-derived suppressor cells mobilization and function in protecting against acute graft-versus-host disease after bone marrow transplantation. PG - 122-131 LID - S1521-6616(17)30050-5 [pii] LID - 10.1016/j.clim.2017.11.005 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Lin, Yu AU - Lin Y AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Institute of Hematology, Zhejiang University, Hangzhou, China. FAU - Wang, Binsheng AU - Wang B AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Shan, Wei AU - Shan W AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Tan, Yamin AU - Tan Y AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Feng, Jingjing AU - Feng J AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Xu, Lin AU - Xu L AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Wang, Limengmeng AU - Wang L AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Institute of Hematology, Zhejiang University, Hangzhou, China. FAU - Han, Biqing AU - Han B AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Zhang, Mingming AU - Zhang M AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Yu, Jian AU - Yu J AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Yu, Xiaohong AU - Yu X AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Huang, He AU - Huang H AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Institute of Hematology, Zhejiang University, Hangzhou, China. Electronic address: huanghe@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171110 PL - United States TA - Clin Immunol JT - Clinical immunology (Orlando, Fla.) JID - 100883537 RN - 0 (Immunosuppressive Agents) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 3.5.3.1 (Arg1 protein, mouse) RN - EC 3.5.3.1 (Arginase) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Arginase/drug effects/metabolism MH - *Bone Marrow Transplantation MH - Cell Differentiation/drug effects MH - Cell Movement/*drug effects MH - Cell Proliferation/drug effects MH - Graft vs Host Disease/*immunology MH - Immunosuppressive Agents/*pharmacology MH - In Vitro Techniques MH - Mice MH - Monocytes/drug effects/immunology MH - Myeloid-Derived Suppressor Cells/*drug effects/immunology MH - Nitric Oxide Synthase Type II/drug effects/metabolism MH - Sirolimus/*pharmacology MH - Spleen MH - T-Lymphocytes, Helper-Inducer/*drug effects/immunology MH - T-Lymphocytes, Regulatory/*drug effects/immunology MH - Th1 Cells/drug effects/immunology MH - Th2 Cells/drug effects/immunology OTO - NOTNLM OT - Acute graft-versus-host disease OT - Polymorphonuclear myeloid-derived suppressor cells OT - Rapamycin OT - Regulatory T cells OT - mTOR inhibitor EDAT- 2017/11/15 06:00 MHDA- 2019/03/19 06:00 CRDT- 2017/11/15 06:00 PHST- 2017/01/23 00:00 [received] PHST- 2017/10/23 00:00 [revised] PHST- 2017/11/09 00:00 [accepted] PHST- 2017/11/15 06:00 [pubmed] PHST- 2019/03/19 06:00 [medline] PHST- 2017/11/15 06:00 [entrez] AID - S1521-6616(17)30050-5 [pii] AID - 10.1016/j.clim.2017.11.005 [doi] PST - ppublish SO - Clin Immunol. 2018 Feb;187:122-131. doi: 10.1016/j.clim.2017.11.005. Epub 2017 Nov 10.