Luo Yin, Jiang Li-Yan, Liao Zhe-Zhen, Wang Yuan-Yuan, Wang Ya-Di, Xiao Xin-Hua
The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Immunology. 2025 Feb;174(2):189-202. doi: 10.1111/imm.13875. Epub 2024 Nov 14.
Itaconic acid and its metabolites have demonstrated significant therapeutic potential in various immune diseases. Originating from the tricarboxylic acid cycle in immune cells, itaconic acid can modulate immune responses, diminish inflammation, and combat oxidative stress. Recent research has uncovered multiple mechanisms through which itaconic acid exerts its effects, including the inhibition of inflammatory cytokine production, activation of anti-inflammatory pathways, and modulation of immune cell function by regulating cellular metabolism. Cellular actions are influenced by the modulation of metabolic pathways, such as inhibiting succinate dehydrogenase (SDH) activity or glycolysis, activation of nuclear-factor-E2-related factor 2 (Nrf2), boosting cellular defences against oxidative stress, and suppression of immune cell inflammation through the NF-κB pathway. This comprehensive review discusses the initiation, progression, and mechanisms of action of itaconic acid and its metabolites, highlighting their modulatory effects on various immune cell types. Additionally, it examines their involvement in immune disease like rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and autoimmune hepatitis, offering greater understanding for creating new therapies for these ailments.
衣康酸及其代谢产物在多种免疫疾病中已显示出显著的治疗潜力。衣康酸源自免疫细胞中的三羧酸循环，可调节免疫反应、减轻炎症并对抗氧化应激。最近的研究发现了衣康酸发挥作用的多种机制，包括抑制炎性细胞因子的产生、激活抗炎途径以及通过调节细胞代谢来调节免疫细胞功能。细胞作用受到代谢途径调节的影响，例如抑制琥珀酸脱氢酶（SDH）活性或糖酵解、激活核因子E2相关因子2（Nrf2）、增强细胞对氧化应激的防御能力以及通过NF-κB途径抑制免疫细胞炎症。这篇综述讨论了衣康酸及其代谢产物的起始、进展和作用机制，强调了它们对各种免疫细胞类型的调节作用。此外，还研究了它们在类风湿性关节炎、多发性硬化症、1型糖尿病和自身免疫性肝炎等免疫疾病中的作用，为开发针对这些疾病的新疗法提供了更深入的理解。
