2. Academic Validation
  3. Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke

Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke

  • Cell Rep. 2023 Jun 6;42(6):112617. doi: 10.1016/j.celrep.2023.112617.
Lei Li 1,  Shu-Qi Cheng 1,  Yu-Qin Sun 1,  Jian-Bing Yu 1,  Xin-Xin Huang 1,  Yin-Feng Dong 2,  Juan Ji 1,  Xi-Yue Zhang 1,  Gang Hu 1,  Xiu-Lan Sun 3
Affiliations

Affiliations

  • 1 Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
  • 2 Nanjing University of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
  • 3 Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China; Nanjing University of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: [email protected].
PMID: 37285269 DOI: 10.1016/j.celrep.2023.112617
Abstract

Neutrophil aggregation and clearance are important factors affecting neuroinflammatory injury during acute ischemic stroke. Emerging evidence suggests that energy metabolism is essential for microglial functions, especially microglial phagocytosis, which determines the degree of brain injury. Here, we demonstrate that Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenic acid (DHA), promotes the phagocytosis of neutrophils by microglia, thereby reducing neutrophil accumulation in the brain and alleviating neuroinflammation in the ischemic brain. Further studies reveal that RvD1 reprograms energy metabolism from glycolysis to oxidative phosphorylation (OXPHOS), providing sufficient energy for microglial phagocytosis. Moreover, RvD1 enhances microglial glutamine uptake and stimulates glutaminolysis to support OXPHOS to boost ATP production depending on adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Overall, our results reveal that RvD1 reprograms energy metabolism to promote the microglial phagocytosis of neutrophils after ischemic stroke. These findings may guide perspectives for stroke therapy from modulating microglial immunometabolism.

Keywords

CP: Immunology; Resolvin D1; immunometabolism; ischemic stroke; microglia; neutrophil; phagocytosis; reprogram energy metabolism.

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