Metabolic Regulation of Inflammation: Exploring the Potential Benefits of Itaconate in Autoimmune Disorders.

IF 4.9 3区医学 Q2 IMMUNOLOGY Immunology Pub Date : 2024-11-14 DOI:10.1111/imm.13875

Yin Luo, Li-Yan Jiang, Zhe-Zhen Liao, Yuan-Yuan Wang, Ya-Di Wang, Xin-Hua Xiao

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Abstract

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.

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炎症的代谢调节：探索伊塔康酸对自身免疫性疾病的潜在益处

衣康酸及其代谢物在治疗各种免疫疾病方面具有显著的潜力。衣康酸来源于免疫细胞中的三羧酸循环，它可以调节免疫反应、减轻炎症反应并对抗氧化应激。最近的研究发现了衣康酸发挥作用的多种机制，包括抑制炎症细胞因子的产生、激活抗炎途径以及通过调节细胞新陈代谢来调节免疫细胞的功能。细胞作用受代谢途径调节的影响，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。这篇综合性综述讨论了衣康酸及其代谢物的起始、发展和作用机制，强调了它们对各种免疫细胞类型的调节作用。此外，还探讨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性疾病中的参与作用，为开发治疗这些疾病的新疗法提供了更深入的理解。

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来源期刊

Immunology 医学-免疫学

CiteScore

11.90

自引率

1.60%

发文量

175

审稿时长

4-8 weeks

期刊介绍： Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.

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