Diabetes Primes Neutrophils for Neutrophil Extracellular Trap Formation through Trained Immunity  

作　　者：Sanjeeb Shrestha Yu-Bin Lee Hoyul Lee Yeon-Kyung Choi Bo-Yoon Park Mi-Jin Kim Young-Jin Youn Sun-Hwa Kim Soo-Jung Jung Dong-Keun Song Hee Kyung Jin Jae-Sung Bae In-Kyu Lee Jae-Han Jeon Chang-Won Hong 

机构地区：[1]Department of Physiology,School of Medicine,Kyungpook National University,Daegu 41944,Republic of Korea [2]Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease,Kyungpook National University Hospital,Daegu 41404,Republic of Korea [3]Research Institute of Aging and Metabolism,Kyungpook National University,Daegu 41404,Republic of Korea [4]Department of Internal Medicine,School of Medicine,Kyungpook National University,Kyungpook National University Chilgok Hospital,Daegu 41404,Republic of Korea [5]Department of Pharmacology,College of Medicine,Hallym University,Chuncheon 24252,Republic of Korea [6]Department of Laboratory Animal Medicine,College of Veterinary Medicine,Kyungpook National University,Daegu 41566,Republic of Korea [7]KNU Alzheimer’s disease Research Institute,Kyungpook National University,Daegu 41566,Republic of Korea [8]Department of Internal Medicine,School of Medicine,Kyungpook National University,Kyungpook National University Hospital,Daegu 41940,Republic of Korea

出　　处：《Research》2024年第4期696-709,共14页研究(英文)

基　　金：supported by National Research Foundation of Korea Grants 2022R1A2C2006898(to C.-W.H.);2020R1A4A2002691(to H.K.J.,J.-S.B.,and C.-W.H.);2020R1C1C1012729(to J.-H.J.);2021H1D3A2A01099688(to S.S.);Biomedical Research Institute Grant from Kyungpook National University Hospital(2018)and the Korean Health Industry Development Institute(KHIDI);funded by the Ministry of Health and Welfare,Republic of Korea(to J.-H.J.and C.-W.H.).

摘　　要：Neutrophils are primed for neutrophil extracellular trap(NET)formation during diabetes,and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes.Here,we demonstrate that trained immunity mediates diabetes-induced NET priming in neutrophils.Under diabetic conditions,neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation,which result in the accumulation of acetyl-coenzyme A.Adenosine 5′-triphosphate-citrate lyase-mediated accumulation of acetyl-coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3(AcH3K9,AcH3K14,and AcH3K27)and histone 4(AcH4K8).The pharmacological inhibition of adenosine 5′-triphosphatecitrate lyase and histone acetyltransferases completely inhibited high-glucose-induced NET priming.The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes.Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments,and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.

关 键 词：IMMUNITY HEALING inhibited 

分 类 号：R58[医药卫生—内分泌]