Frontiers in Cell and Developmental Biology (Dec 2021)
mTOR Signaling Regulates the Development and Therapeutic Efficacy of PMN-MDSCs in Acute GVHD
- Xiaoqing Li,
- Xiaoqing Li,
- Xiaoqing Li,
- Xiaoqing Li,
- Yixue Li,
- Yixue Li,
- Yixue Li,
- Yixue Li,
- Qinru Yu,
- Qinru Yu,
- Qinru Yu,
- Qinru Yu,
- Lin Xu,
- Lin Xu,
- Lin Xu,
- Lin Xu,
- Shan Fu,
- Shan Fu,
- Shan Fu,
- Shan Fu,
- Cong Wei,
- Cong Wei,
- Cong Wei,
- Cong Wei,
- Limengmeng Wang,
- Limengmeng Wang,
- Limengmeng Wang,
- Limengmeng Wang,
- Yi Luo,
- Yi Luo,
- Yi Luo,
- Yi Luo,
- Jimin Shi,
- Jimin Shi,
- Jimin Shi,
- Jimin Shi,
- Pengxu Qian,
- Pengxu Qian,
- Pengxu Qian,
- He Huang,
- He Huang,
- He Huang,
- He Huang,
- Yu Lin,
- Yu Lin,
- Yu Lin,
- Yu Lin
Affiliations
- Xiaoqing Li
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Xiaoqing Li
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Xiaoqing Li
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Xiaoqing Li
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Yixue Li
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Yixue Li
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Yixue Li
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Yixue Li
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Qinru Yu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Qinru Yu
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Qinru Yu
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Qinru Yu
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Lin Xu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Lin Xu
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Lin Xu
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Lin Xu
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Shan Fu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Shan Fu
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Shan Fu
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Shan Fu
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Cong Wei
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Cong Wei
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Cong Wei
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Cong Wei
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Limengmeng Wang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Limengmeng Wang
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Limengmeng Wang
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Limengmeng Wang
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Yi Luo
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Yi Luo
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Yi Luo
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Yi Luo
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Jimin Shi
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jimin Shi
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Jimin Shi
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Jimin Shi
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Pengxu Qian
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Pengxu Qian
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Pengxu Qian
- Institute of Hematology, Zhejiang University, Hangzhou, China
- He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- He Huang
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- He Huang
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- He Huang
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Yu Lin
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Yu Lin
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Yu Lin
- Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Yu Lin
- Institute of Hematology, Zhejiang University, Hangzhou, China
- DOI
- https://doi.org/10.3389/fcell.2021.741911
- Journal volume & issue
-
Vol. 9
Abstract
Myeloid-derived suppressor cells (MDSCs) represent a population of heterogeneous myeloid cells, which are characterized by their remarkable ability to suppress T cells and natural killer cells. MDSCs have been proven to play a positive role in protecting acute graft-versus-host disease (aGVHD). Here, we aimed to describe the mechanism behind how mTOR signaling regulates MDSCs’ generation and explore its prophylactic and therapeutic potential in aGVHD. Reducing mTOR expression retains myeloid cells with immature characteristics and promotes polymorphonuclear MDSC (PMN-MDSC) immunosuppressive function through STAT3-C/EBPβ pathway. Prophylactic transfusion of mTORKO PMN-MDSCs could alleviate aGVHD while maintaining the graft-versus-leukemia (GVL) effect, which could downregulate the Th1/Th2 ratio, decrease serum proinflammatory cytokines, and increase the proportion of regulatory T cells (Tregs) in aGVHD models at the early stage after transplantation. Moreover, transfusion therapy could promote the reconstruction and function of donor-derived PMN-MDSCs. Not only the percentage and the absolute number of donor-derived PMN-MDSCs significantly increased but also the immunosuppressive ability was much more robust compared to other groups. Altogether, these findings indicated that mTOR is an intrinsic regulator for PMN-MDSCs’ differentiation and immunosuppressive function. Together, mTORKO PMN-MDSC transfusion can play a protective role in alleviating cytokine storm at the initial stage and promoting the quantitative and functional recoveries of donor-derived PMN-MDSCs in aGVHD.
Keywords
