ArticleNature cell biology2022
Itaconate inhibits TET DNA dioxygenases to dampen inflammatory responses.
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Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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129citing papers in PubMed
15.3field-weighted citation impact, top 1% of its field
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Who cites it
129 citing papers in PubMed, 196 citations in OpenAlex.
- Robust structural, kinetic and biophysical characterization of wild-type human ACOD1, selected mutants and their interaction with citraconate.Journal of structural biology: X · 2026Article
- Itaconate as the endogenous brake of proinflammatory macrophage activation alleviates inflammation in liver fibrogenesis.Hepatology communications · 2026Article
- Hepatic control of immunometabolism: implications for the pathogenesis, diagnosis and treatment of rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- TET2-driven demethylation of ANG promotes angiogenesis and malignant transformation in oligodendroglioma.Oncogene · 2026Article
- Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026Review
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Microparticles synthesized from itaconate polyesters enable metabolite delivery and elicit immunoregulatory outcomes.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- TET2 aggravates podocyte mitotic catastrophe and renal injury in diabetic nephropathy via m5C-dependent downregulation of Wee1 and activation of CDK1-cyclinB1 signaling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Review
- TET2 as a Context-Dependent Epigenetic Integrator in Clonal Hematopoiesis, Inflammation, Cancer, and Immunotherapy.Cell biochemistry and function · 2026Review
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Four-Octyl Itaconate Alleviates Enterococcus faecalis-Induced Apical Periodontitis by Inhibiting Macrophage M1 Polarisation.International endodontic journal · 2026Article
- Offense and defense: itaconate mediates bidirectional immune regulation of host-bacteria interaction.Journal of biomedical science · 2026Review
- Oncometabolite 2-hydroxyglutarate destabilizes CDH1 to regulate quiescence and enhance chemotherapy sensitivity.Cell communication and signaling : CCS · 2026Article
- Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells.Cell metabolism · 2026Article
- Metabolic pattern changes of macrophages during cancer development and progression.Journal of translational medicine · 2026Review
- CD73Nature communications · 2026Article
- Article
- Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026Review
69 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 8 institutions in 3 countries.
Lei-Lei Chen *Huashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Carmen Morcelle *Huashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-3895-5852
Zhou-Li Cheng *Huashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Xiufei ChenHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Yanping XuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2750-5466
Yajing GaoHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-1639-7909
Junbin SongHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Zhijun LiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Matthew D SmithLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Miao ShiLife Sciences Institute and Stem Cell Institute, Zhejiang University, Hangzhou, China.
Yezhang ZhuLife Sciences Institute and Stem Cell Institute, Zhejiang University, Hangzhou, China.
Neng ZhouKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University of Medicine, Shanghai, China.
Meng ChengLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-4137-903X
Chenxi HeHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Kwei-Yan LiuHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Guoping LuDepartment of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China.
Lei ZhangHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Cheng ZhangHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-9218-5019
Jinye ZhangHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-8947-2607
Yiping SunHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Tuan QiKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Yingying LyuDepartment of Neurosurgery, Huashan Hospital, Fudan Universit, Shanghai, China.
Zhi-Zhong RenLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Xian-Ming TanLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jiayong YinHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Fei LanHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Ying LiuDepartment of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.
Hui YangDepartment of Neurosurgery, Huashan Hospital, Fudan Universit, Shanghai, China.ORCID http://orcid.org/0000-0002-2865-5311
Maoxiang QianHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Caiwen DuanKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University of Medicine, Shanghai, China.
Xing ChangKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Yufeng ZhouHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-6050-4951
Li ShenLife Sciences Institute and Stem Cell Institute, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0002-5696-2191
Albert S BaldwinLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kun-Liang GuanDepartment of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, USA.
Yue XiongLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Dan YeHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China. yedan@fudan.edu.cn.ORCID http://orcid.org/0000-0003-4848-0501
Shanghai Medical College of Fudan University · CNUniversity of North Carolina at Chapel Hill · USZhejiang University · CNHuashan Hospital · CNShanghai Jiao Tong University · CNWestlake University · CNChildren's Hospital of Fudan University · CNUniversity of California San Diego · US
Funding
Mechanisms of Metabolic Gene Mutations in CancerR01CA163834 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 2012 to 2023
$3.1MNCI NIH HHS R01 CA163834
Abstract
As one of the most induced genes in activated macrophages, immune-responsive gene 1 (IRG1) encodes a mitochondrial metabolic enzyme catalysing the production of itaconic acid (ITA). Although ITA has an anti-inflammatory property, the underlying mechanisms are not fully understood. Here we show that ITA is a potent inhibitor of the TET-family DNA dioxygenases. ITA binds to the same site on TET2 as the co-substrate α-ketoglutarate, inhibiting TET2 catalytic activity. Lipopolysaccharide treatment, which induces Irg1 expression and ITA accumulation, inhibits Tet activity in macrophages. Transcriptome analysis reveals that TET2 is a major target of ITA in suppressing lipopolysaccharide-induced genes, including those regulated by the NF-κB and STAT signalling pathways. In vivo, ITA decreases the levels of 5-hydroxymethylcytosine, reduces lipopolysaccharide-induced acute pulmonary oedema as well as lung and liver injury, and protects mice against lethal endotoxaemia, depending on the catalytic activity of Tet2. Our study thus identifies ITA as an immune modulatory metabolite that selectively inhibits TET enzymes to dampen the inflammatory responses.
Indexed as
DioxygenasesAnimalsDNALipopolysaccharidesMiceSuccinatesDioxygenasesDNAitaconic acidLipopolysaccharidesSuccinates
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