谷氨酰胺分解
重编程
谷氨酰胺
表观遗传学
巨噬细胞
新陈代谢
细胞生物学
生物
免疫系统
谷氨酰胺酶
生物化学
免疫学
细胞
基因
体外
氨基酸
作者
Po‐Tsun Liu,Hai‐Ping Wang,Xiaoyun Li,Tung Chao,Tony Teav,Stefan Christen,Giusy Di Conza,Wan-Chen Cheng,Chih‐Hung Chou,Magdaléna Vaváková,Charlotte Muret,Koen Debackere,Massimiliano Mazzone,Hsien‐Da Huang,Sarah‐Maria Fendt,Julijana Ivanišević,Ping‐Chih Ho
摘要
How glutamine metabolism orchestrates macrophage activation is unclear. Ho and colleagues show glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming. Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages. As such, αKG contributes to endotoxin tolerance after M1 activation. This study reveals new mechanistic regulations by which glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming.
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