三羧酸 (TCA) 循环代谢物与调节免疫细胞的信号通路有关。值得注意的例子包括琥珀酸和衣康酸，它们分别具有促炎和抗炎作用。最近，富马酸盐在巨噬细胞激活中具有特定作用，调节白细胞介素 (IL)-10 和 I 型干扰素 (IFN) 等细胞因子的产生。富马酸水合酶 (FH) 已被确定为控制点。值得注意的是，不同模型和细胞类型中的 FH 丢失会导致线粒体释放 DNA 和 RNA，这些核酸传感器可被胞质核酸传感器感知，包括视黄酸诱导基因 (RIG)-I、黑色素瘤分化相关蛋白 (MDA) 5、环 GMP-AMP 合酶 (cGAS) 上调 IFN-β 的产生。这些发现可能与 FH 水平降低相关疾病的发病机制和治疗相关，例如系统性红斑狼疮 (SLE) 或 FH 缺陷性肾癌。版权所有 © 2023 Elsevier Ltd。保留所有权利。

Tricarboxylic acid (TCA) cycle metabolites have been implicated in modulating signalling pathways in immune cells. Notable examples include succinate and itaconate, which have pro- and anti-inflammatory roles, respectively. Recently, fumarate has emerged as having specific roles in macrophage activation, regulating the production of such cytokines as interleukin (IL)-10 and type I interferons (IFNs). Fumarate hydratase (FH) has been identified as a control point. Notably, FH loss in different models and cell types has been found to lead to DNA and RNA release from mitochondria which are sensed by cytosolic nucleic acid sensors including retinoic acid-inducible gene (RIG)-I, melanoma differentiation-associated protein (MDA)5, and cyclic GMP-AMP synthase (cGAS) to upregulate IFN-β production. These findings may have relevance in the pathogenesis and treatment of diseases associated with decreased FH levels such as systemic lupus erythematosus (SLE) or FH-deficient kidney cancer.Copyright © 2023 Elsevier Ltd. All rights reserved.