生物
柠檬酸循环
促炎细胞因子
细胞生物学
效应器
巨噬细胞
基因表达调控
免疫系统
代谢途径
炎症
新陈代谢
生物化学
基因
免疫学
体外
作者
Dylan Gerard Ryan,Luke A. J. O’Neill
出处
期刊:Annual Review of Immunology
[Annual Reviews]
日期:2020-04-26
卷期号:38 (1): 289-313
被引量:243
标识
DOI:10.1146/annurev-immunol-081619-104850
摘要
A striking change has happened in the field of immunology whereby specific metabolic processes have been shown to be a critical determinant of immune cell activation. Multiple immune receptor types rewire metabolic pathways as a key part of how they promote effector functions. Perhaps surprisingly for immunologists, the Krebs cycle has emerged as the central immunometabolic hub of the macrophage. During proinflammatory macrophage activation, there is an accumulation of the Krebs cycle intermediates succinate and citrate, and the Krebs cycle–derived metabolite itaconate. These metabolites have distinct nonmetabolic signaling roles that influence inflammatory gene expression. A key bioenergetic target for the Krebs cycle, the electron transport chain, also becomes altered, generating reactive oxygen species from Complexes I and III. Similarly, alternatively activated macrophages require α-ketoglutarate-dependent epigenetic reprogramming to elicit anti-inflammatory gene expression. In this review, we discuss these advances and speculate on the possibility of targeting these events therapeutically for inflammatory diseases.
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