The IRG1-Itaconate axis: A regulatory hub for immunity and metabolism in macrophages.

IF 4.3 4区 医学 Q2 IMMUNOLOGY
Yangguang Li, Wenbin Gong, Weizhen Li, Peizhao Liu, Juanhan Liu, Haiyang Jiang, Tao Zheng, Jie Wu, Xiuwen Wu, Yun Zhao, Jianan Ren
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引用次数: 9

Abstract

Metabolism could be served as a guiding force for immunity, and macrophages undergo drastic metabolic reprogramming during inflammatory processes, including enhancing glycolysis and reshaping the tricarboxylic acid cycle (TCA) cycle. The disrupted TCA cycle facilitates itaconate accumulation, consistent with the significant up-regulation of immune response gene 1 (IRG1) in activated macrophages. IRG1 catalyzes the decarboxylation of cis-aconitate to synthesize itaconate, and notably, the IRG1-Itaconate axis has excellent potential to link macrophages' immunity and metabolism. Here, we review vital molecules that affect the activation of the IRG1-Itaconate axis, including interferon regulatory factor 1/9 (IRF1/9), transcription 1 and 3 (STAT1/3), CCAAT enhancer-binding protein β (C/EBPβ), and the protein kinase C (PKC). We then focus on how the IRG1-Itaconate axis regulates the inflammatory pathway in macrophages, proposed to involve kelch-like ECH-associated protein 1 (Keap1), NOD-, LRR- and pyrin domain-containing 3 (NLRP3), gasdermin D (GSDMD), activating transcription factor 3 (ATF3), receptor-interacting protein kinase-3 (RIPK3), et al. In addition, we provide an overview of the way the axis participates in the metabolism of macrophages. Eventually, we summarize current connections between the IRG1-Itaconate axis and inflammatory diseases, bringing light to new therapeutic opportunities in inflammatory diseases.

irg1 -衣康酸轴:巨噬细胞免疫和代谢的调节枢纽。
代谢可以作为免疫的指导力量,巨噬细胞在炎症过程中进行剧烈的代谢重编程,包括增强糖酵解和重塑三羧酸循环(TCA)循环。TCA循环的中断促进了衣康酸的积累,这与激活的巨噬细胞中免疫应答基因1 (IRG1)的显著上调一致。IRG1催化顺式乌头酸脱羧合成衣康酸,值得注意的是,IRG1-衣康酸轴具有连接巨噬细胞免疫和代谢的极好潜力。在这里,我们回顾了影响irg1 -衣康酸轴激活的重要分子,包括干扰素调节因子1/9 (IRF1/9)、转录1和3 (STAT1/3)、CCAAT增强子结合蛋白β (C/EBPβ)和蛋白激酶C (PKC)。然后,我们重点研究了IRG1-Itaconate轴如何调节巨噬细胞的炎症途径,提出涉及kelch样ech相关蛋白1 (Keap1), NOD-, LRR-和pyrin结构域3 (NLRP3), gasdermin D (GSDMD),激活转录因子3 (ATF3),受体相互作用蛋白激酶3 (RIPK3)等。此外,我们还概述了轴参与巨噬细胞代谢的方式。最后,我们总结了irg1 -衣康酸轴与炎症性疾病之间的联系,为炎症性疾病的治疗带来新的机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.00
自引率
4.00%
发文量
24
期刊介绍: This review journal provides the most current information on basic and translational research in immunology and related fields. In addition to invited reviews, the journal accepts for publication articles and editorials on relevant topics proposed by contributors. Each issue of International Reviews of Immunology contains both solicited and unsolicited review articles, editorials, and ''In-this-Issue'' highlights. The journal also hosts reviews that position the authors'' original work relative to advances in a given field, bridging the gap between annual reviews and the original research articles. This review series is relevant to all immunologists, molecular biologists, microbiologists, translational scientists, industry researchers, and physicians who work in basic and clinical immunology, inflammatory and allergic diseases, vaccines, and additional topics relevant to medical research and drug development that connect immunology to disciplines such as oncology, cardiovascular disease, and metabolic disorders. Covered in International Reviews of Immunology: Basic and developmental immunology (innate and adaptive immunity; inflammation; and tumor and microbial immunology); Clinical research (mechanisms of disease in man pertaining to infectious diseases, autoimmunity, allergy, oncology / immunology); and Translational research (relevant to biomarkers, diagnostics, vaccines, and drug development).
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