ArticleNature metabolism2025
Itaconate modulates immune responses via inhibition of peroxiredoxin 5.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- Metabolic hallmarks of regulated cell death.Cell research · 2026Review
- 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
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- Mesenchymal Stromal Cells in Immunometabolic Regulation: A Review of Itaconate-Mediated Mechanisms.Stem cell reviews and reports · 2026Review
- Offense and defense: itaconate mediates bidirectional immune regulation of host-bacteria interaction.Journal of biomedical science · 2026Review
- The alkylation of AIM2 by itaconate mediates macrophage PANoptosis during sepsis.Cellular & molecular immunology · 2026Article
- Connexin Regulation and Modulation of Neural Stem Cell Differentiation Induced by Cell-Permeable Itaconate.Journal of cellular physiology · 2026Article
- Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026Review
- Mitochondrial iNOS blocks itaconate production by interacting with IRG1.Nature metabolism · 2026Article
- Metabolic control of neuroinflammation: focus on itaconate and its derivatives in CNS disorders.Frontiers in immunology · 2026Review
- Rewiring macrophage immunometabolism in gouty arthritis: from metabolic checkpoints to intelligent nano-delivery.Frontiers in pharmacology · 2026Review
- Article
- Airway immunometabolic responses during pulmonary bacterial and viral infections.Cell reports · 2025Review
- IER3 drives the transition from sepsis-associated AKI to CKD by suppressing the mitochondrial translocation of PRDX5.Cellular and molecular life sciences : CMLS · 2025Article
- Dissecting antimicrobial logic: species-specific strategies for intracellular pathogen defense.mSphere · 2025Review
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Itaconate boosts type I IFN response by disrupting cytoprotection.Nature metabolism · 2025Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
The immunoregulatory metabolite itaconate accumulates in innate immune cells upon Toll-like receptor stimulation. In response to macrophage activation by lipopolysaccharide, itaconate inhibits inflammasome activation and boosts type I interferon signalling; however, the molecular mechanism of this immunoregulation remains unclear. Here, we show that the enhancement of type I interferon secretion by itaconate depends on the inhibition of peroxiredoxin 5 and on mitochondrial reactive oxygen species. We find that itaconate non-covalently inhibits peroxiredoxin 5, leading to the modulation of mitochondrial peroxide in activating macrophages. Through genetic manipulation, we confirm that peroxiredoxin 5 modulates type I interferon secretion in macrophages. The non-electrophilic itaconate mimetic 2-methylsuccinate inhibits peroxiredoxin 5 and phenocopies immunoregulatory action of itaconate on type I interferon and inflammasome activation, providing further support for a non-covalent inhibition of peroxiredoxin 5 by itaconate. Our work provides insight into the molecular mechanism of actions and biological rationale for the predominantly immune specification of itaconate.
Indexed as
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40251412What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.