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Glycolysis inhibition ameliorates brain injury after ischemic stroke by promoting the function of myeloid-derived suppressor cells.
Yan, Jingwei; Li, Anqi; Chen, Xianglin; Cao, Kaixiang; Song, Mingchuan; Guo, Shuai; Li, Zou; Huang, Shuqi; Li, Ziling; Xu, Danghan; Wang, Yong; Dai, Xiaoyan; Feng, Du; Huo, Yuqing; He, Jun; Xu, Yiming.
Afiliación
  • Yan J; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Li A; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Chen X; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China.
  • Cao K; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Song M; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Guo S; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Li Z; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Huang S; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Li Z; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Xu D; Department of Rehabilitation Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Wang Y; College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
  • Dai X; Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • Feng D; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
  • Huo Y; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, USA.
  • He J; Department of Rehabilitation Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: hejunzj@gzucm.edu.cn.
  • Xu Y; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou,
Pharmacol Res ; 179: 106208, 2022 05.
Article en En | MEDLINE | ID: mdl-35398239
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells which are immunosuppressive and glycolytically inactive in inflammatory diseases. However, it is unknown whether MDSCs contribute to ischemic stroke and how glycolysis regulates MDSC function in such a context. Here, we showed that MDSCs arise in the blood of patients at early phase of stroke. Similar results were observed in temporary middle cerebral artery occlusion-induced cerebral ischemic mice. Pharmaceutical exhaustion of MDSCs aggravated, while adoptive transfer of MDSCs rescued the ischemic brain injury. However, the differentiation of MDSCs into immunopotent myeloid cells which coincides with increased glycolysis was observed in the context of ischemic stroke. Mechanistically, the glycolytic product lactate autonomously induces MDSC differentiation through activation of mTORC1, and paracrinely activates Th1 and Th17 cells. Moreover, gene knockout or inhibition of the glycolytic enzyme PFKFB3 increased endogenous MDSCs by blocking their differentiation, and improved ischemic brain injury. Collectively, these results revealed that glycolytic switch decreases the immunosuppressive and neuroprotective role of MDSCs in ischemic stroke and pharmacological targeting MDSCs via glycolysis inhibition constitutes a promising therapeutic strategy for ischemic stroke.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Células Supresoras de Origen Mieloide / Accidente Cerebrovascular Isquémico Límite: Animals / Humans Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Células Supresoras de Origen Mieloide / Accidente Cerebrovascular Isquémico Límite: Animals / Humans Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos