Immune cells undergo rapid and extensive metabolic changes during inflammation. In addition to contributing to energetic and biosynthetic demands, metabolites can also function as signaling molecules. Itaconate (ITA) rapidly accumulates to high levels in myeloid cells under infectious and sterile inflammatory conditions. This metabolite binds to and regulates the function of diverse proteins intracellularly to influence metabolism, oxidative response, epigenetic modification, and gene expression and to signal extracellularly through binding the G protein-coupled receptor (GPCR). Administration of ITA protects against inflammatory diseases and blockade of ITA production enhances antitumor immunity in preclinical models. In this article, we review ITA metabolism and its regulation, discuss its target proteins and mechanisms, and conjecture a rationale for developing ITA-based therapeutics to treat inflammatory diseases and cancer.

中文翻译：

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衣康酸在宿主炎症和防御中的作用

免疫细胞在炎症过程中经历快速而广泛的代谢变化。除了满足能量和生物合成需求外，代谢物还可以充当信号分子。在感染性和无菌炎症条件下，衣康酸 (ITA) 在骨髓细胞中迅速积累至高水平。该代谢物结合并调节细胞内多种蛋白质的功能，以影响代谢、氧化反应、表观遗传修饰和基因表达，并通过结合 G 蛋白偶联受体 (GPCR) 向细胞外发出信号。在临床前模型中，施用 ITA 可预防炎症性疾病，而阻断 ITA 的产生可增强抗肿瘤免疫力。在本文中，我们回顾了 ITA 代谢及其调控，讨论了其靶蛋白和机制，并推测了开发基于 ITA 的疗法来治疗炎症性疾病和癌症的基本原理。