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.

中文翻译：

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巨噬细胞免疫代谢中的克雷布斯循环重生。

免疫学领域发生了惊人的变化，其中特定的代谢过程已被证明是免疫细胞激活的关键决定因素。多种免疫受体类型重新连接代谢途径，作为它们如何促进效应子功能的关键部分。也许令免疫学家感到惊讶的是，克雷布斯循环已成为巨噬细胞的中央免疫代谢中心。在促炎巨噬细胞激活过程中，三羧酸循环中间体琥珀酸和柠檬酸以及三羧酸循环衍生的代谢物衣康酸会积累。这些代谢物具有影响炎症基因表达的独特非代谢信号作用。克雷布斯循环的一个关键生物能量目标，即电子传递链，也发生了改变，从复合物 I 和 III 中产生活性氧。相似地，替代激活的巨噬细胞需要α-酮戊二酸依赖性表观遗传重编程来引发抗炎基因表达。在这篇综述中，我们讨论了这些进展，并推测了针对炎症性疾病治疗这些事件的可能性。