Itaconate: A key regulator of immune responses and potential therapeutic target for autoimmune and inflammatory diseases

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews Pub Date : 2025-07-17 DOI:10.1016/j.autrev.2025.103885

Yutong Liu , Xueling Jiang , Songnian Zhuang , Lihua Zhu , Bo Zhu , Ke Rui , Jie Tian

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Abstract

Itaconate, a metabolite of the tricarboxylic acid cycle (TAC), has gained increasing attention in recent years due to its anti-inflammatory and immunomodulatory properties. It plays a crucial role in immune regulation by modulating signal transduction and posttranslational modification. Itaconate is derived from cis-aconitate decarboxylation and is produced by cis-aconitate decarboxylase (ACOD1) in the mitochondria. During cellular stress conditions, itaconate rapidly accumulates in myeloid cells. Recent studies have demonstrated that itaconate plays a pivotal role in modulating both innate and adaptive immune responses. Moreover, itaconate regulates the differentiation and function of innate immune and lymphoid cells, which is implicated in the pathogenesis of autoimmune diseases. In this review, we aim to explore the recent advancements in comprehending the functional regulation and mechanisms of itaconate in various populations of innate immune and lymphoid cells, as well as its immunomodulatory effects in the development of autoimmune diseases. In addition, we highlight the potential therapeutic applications of itaconate and its derivatives in autoimmune diseases.

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衣康酸：免疫反应的关键调节剂和自身免疫性和炎症性疾病的潜在治疗靶点

衣康酸酯是三羧酸循环（TAC）的代谢物，近年来因其抗炎和免疫调节的特性而受到越来越多的关注。它通过调节信号转导和翻译后修饰在免疫调节中起重要作用。衣康酸来源于顺式乌头酸脱羧，由线粒体中的顺式乌头酸脱羧酶（ACOD1）产生。在细胞应激条件下，衣康酸在髓细胞中迅速积累。最近的研究表明衣康酸在调节先天和适应性免疫反应中起关键作用。此外，衣康酸调节先天免疫细胞和淋巴样细胞的分化和功能，这与自身免疫性疾病的发病机制有关。本文就衣康酸在不同先天免疫细胞和淋巴样细胞中的功能调控、机制及其在自身免疫性疾病发生中的免疫调节作用等方面的研究进展进行综述。此外，我们强调衣康酸及其衍生物在自身免疫性疾病中的潜在治疗应用。

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来源期刊

Autoimmunity reviews 医学-免疫学

CiteScore

24.70

自引率

4.40%

发文量

164

审稿时长

21 days

期刊介绍： Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.