Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke
Lei Li,
Shu-Qi Cheng,
Yu-Qin Sun,
Jian-Bing Yu,
Xin-Xin Huang,
Yin-Feng Dong,
Juan Ji,
Xi-Yue Zhang,
Gang Hu,
Xiu-Lan Sun
Affiliations
Lei Li
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Shu-Qi Cheng
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Yu-Qin Sun
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Jian-Bing Yu
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Xin-Xin Huang
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Yin-Feng Dong
Nanjing University of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
Juan Ji
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Xi-Yue Zhang
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Gang Hu
Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China
Xiu-Lan Sun
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; Corresponding author
Summary: 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.
