《生命科学》 2022, 34(5): 532-542

三羧酸循环中间产物调控炎症和免疫的研究进展

冯金龙 , 罗　培 , 袁业现 , 束　刚 , 江青艳^*

华南农业大学动物科学学院，农业部华南动物营养与饲料科学观测试验站，广东省动物营养调控重点实验室，广州 510640

摘　要：

适当的炎症反应和免疫应答在病原识别、抵御病原体入侵和清除内部环境危险因素方面起着重要作用。免疫细胞的代谢重编程不仅能满足其对能量产生效率的需求，而且也会促进多种代谢中间产物的累积和释放。这种代谢路径的重塑可以促进免疫细胞在感染、自身免疫、癌症过程中的功能。三羧酸循环是连接碳水化合物代谢、蛋白质代谢和脂质代谢的枢纽。近年来一系列的研究发现，炎症反应和免疫应答过程中会释放出多种三羧酸循环代谢中间产物。这些中间代谢物和衍生物也被证明具有一种非代谢的信号传递功能，如调节先天免疫和适应性免疫细胞的激活，以及促炎介质或抗炎介质的生成。该文总结了免疫细胞代谢重编程、三羧酸循环中间代谢物( 柠檬酸、琥珀酸、延胡索酸、α- 酮戊二酸) 及其衍生物( 衣康酸)对免疫应答和炎症反应的调节作用，为缓解组织局部炎症和调节机体免疫机能的靶向营养调控方案的制定提供参考。

通讯作者：江青艳 , Email:qyjiang@scau.edu.cn

Research progress on the role of TCA cycle intermediate metabolites in inflammation and immunity

FENG Jin-Long , LUO Pei , YUAN Ye-Xian , SHU Gang , JIANG Qing-Yan^*

Guangdong Provincial Key Laboratory of Animal Nutrition Control, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South China (Ministry of Agriculture), College of Animal Science, South China Agricultural University, Guangzhou 510640, China

Abstract:

Appropriate inflammation and immune response play an important role in pathogen recognition, resistance to pathogen invasion, and clearance of internal environmental risk factors. The metabolic reprogramming of immune cells not only meets their requirement for energy supply efficiency, but also promotes the accumulation and release of various metabolic intermediate products, thus enhancing the efficacy of immune cells in infection, autoimmune, and cancer processes. The tricarboxylic acid cycle is the hub linking carbohydrate metabolism, protein metabolism, and lipid metabolism. In recent years, studies have found that inflammation and immune response can release various intermediate metabolites and/or derivatives in the TCA cycle, and they play nonmetabolic signaling roles, including modulating activation of a variety of innate and adaptive immune cells, as well as proinflammatory or anti-inflammatory mediators. This review summarizes the TCA cycle reprogramming, and the regulation of intermediate metabolites (citrate, succinate, fumarate, α-ketoglutarate) and its derivatives (itaconate) on inflammation and immune response, so as to provide a basis for developing targeted nutrition regulation program to alleviate local inflammation and regulate immune function.

Communication Author：JIANG Qing-Yan , Email:qyjiang@scau.edu.cn