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Inhibition of hexokinase 2 with 3-BrPA promotes MDSCs differentiation and immunosuppressive function

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收录情况： ◇ SCIE

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单位： [1]Department of Cardiothoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2]Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [3]Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China [4]Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China [5]Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

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关键词： Hexokinase 2 3-bromopyruvic acid Myeloid-derived suppressor cells Allogeneic heart transplant STAT3 Cellular therapy

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The adoptive transfer of ex vivo generated myeloid-derived suppressor cells (MDSCs) may be a promising therapeutic strategy for preventing allograft rejection after solid organ transplantation. Currently, the precise role of immune-metabolic pathways in the differentiation and function of MDSCs is not fully understood. Hexokinase 2 (HK2) is an isoform of hexokinase and is a key enzyme involved in the increased aerobic glycolysis of different immune cells during their activation and function. Here, we demonstrate that the addition of HK2 inhibitor 3-Bromopyruvic acid (3-BrPA) into traditional MDSCs induction system in vitro significantly promoted MDSCs production and enhanced their immunosuppressive function. Treatment with 3-BrPA increased the expression of MDSC-related immunosuppressive molecules, such as iNOS, Arg1, and CXCR2. Moreover, the adoptive transfer of 3-BrPA-treated MDSCs significantly prolonged the survival time of mouse heart allografts. This study provides a novel strategy to solve the problems of harvesting enough autologous cells for MDSC production from sick patients, and producing functionally enhanced MDSCs for preventing graft rejection and inducing tolerance.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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出版当年[2022]版：

大类 | 4 区医学

小类 | 4 区免疫学 4 区细胞生物学

最新[2025]版：

大类 | 3 区医学

小类 | 4 区细胞生物学 4 区免疫学

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出版当年[2021]版：

Q3 CELL BIOLOGY Q3 IMMUNOLOGY

最新[2023]版：

Q2 CELL BIOLOGY Q2 IMMUNOLOGY

影响因子： 3.7 最新[2023版] 4.1 最新五年平均 4.178 出版当年[2021版] 4.669 出版当年五年平均 4.868 出版前一年[2020版] 4.3 出版后一年[2022版]

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第一作者单位： [1]Department of Cardiothoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

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