Itaconate in host inflammation and defense

Dan Ye; Pu Wang; Lei-Lei Chen; Kun-Liang Guan; Yue Xiong

doi:10.1016/j.tem.2024.02.004

Itaconate in host inflammation and defense

Trends Endocrinol Metab. 2024 Mar 5:S1043-2760(24)00033-X. doi: 10.1016/j.tem.2024.02.004. Online ahead of print.

Authors

Dan Ye¹, Pu Wang², Lei-Lei Chen², Kun-Liang Guan³, Yue Xiong⁴

Affiliations

¹ Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China. Electronic address: yedan@fudan.edu.cn.
² Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
³ School of Life Sciences, Westlake University, Hangzhou, China.
⁴ Cullgen Inc., 12730 High Bluff Drive, San Diego, CA 92130, USA. Electronic address: yue.xiong@cullgen.com.

PMID: 38448252
DOI: 10.1016/j.tem.2024.02.004

Abstract

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.

Keywords: IRG1/ACOD1; cancer; inflammatory diseases; itaconate.

Publication types

Review