1. mTOR inhibitor rapamycin induce polymorphonuclear myeloid-derived suppressor cells mobilization and function in protecting against acute graft-versus-host disease after bone marrow transplantation.
- Author
-
Lin Y, Wang B, Shan W, Tan Y, Feng J, Xu L, Wang L, Han B, Zhang M, Yu J, Yu X, and Huang H
- Subjects
- Animals, Arginase drug effects, Arginase metabolism, Cell Differentiation drug effects, Cell Proliferation drug effects, In Vitro Techniques, Mice, Monocytes drug effects, Monocytes immunology, Myeloid-Derived Suppressor Cells immunology, Nitric Oxide Synthase Type II drug effects, Nitric Oxide Synthase Type II metabolism, Spleen, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Regulatory immunology, Th1 Cells drug effects, Th1 Cells immunology, Th2 Cells drug effects, Th2 Cells immunology, Bone Marrow Transplantation, Cell Movement drug effects, Graft vs Host Disease immunology, Immunosuppressive Agents pharmacology, Myeloid-Derived Suppressor Cells drug effects, Sirolimus pharmacology, T-Lymphocytes, Helper-Inducer drug effects, T-Lymphocytes, Regulatory drug effects
- Abstract
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., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF