中性粒细胞胞外陷阱
存水弯(水管)
免疫学
免疫
细胞外
糖尿病
先天免疫系统
生物
医学
免疫系统
炎症
细胞生物学
物理
内分泌学
气象学
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,Hoyul Lee,Jae‐Han Jeon,Chang-Won Hong
出处
期刊:Research
[AAAS00]
日期:2024-01-01
卷期号:7
被引量:1
标识
DOI:10.34133/research.0365
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′-triphosphate-citrate 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.
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