ArticleJournal of immunology (Baltimore, Md. : 1950)2022
The Immunomodulatory Enzyme IDO2 Mediates Autoimmune Arthritis through a Nonenzymatic Mechanism.
Article in Journal of immunology (Baltimore, Md. : 1950), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Compensatory pathways in tryptophan metabolism and immune regulation following IDO inhibition.Molecular biology reports · 2026Review
- Chicken IDO2 and TDO2: Biochemical Characteristics and Regulatory Roles in Avian Tryptophan Metabolism and Inflammatory Response.Animals : an open access journal from MDPI · 2026Article
- Human IDO2 exhibits unique binding affinities distinct to those of human IDO1.The FEBS journal · 2026Article
- Multi-Omics Analysis Identifies Tryptophan Metabolism and Glycolysis as Potential Pathways Involved in the Protective Effects of Tormentic Acid Against Metabolic Associated Fatty Liver Disease.Pharmacology research & perspectives · 2026Article
- IDO family: the metabolic crossroads connecting immunity, nerves and tumors.Journal of translational medicine · 2026Review
- Roles and mechanisms ofVirulence · 2025Article
- Ido1 or Ido2 deficiency in myeloid-derived cells attenuates TMEV-induced ictogenesis.Journal of neuroimmunology · 2025Article
- Microglia-specific Ido2 deficiency attenuates ictogenesis in the TMEV model of viral encephalitis.Brain, behavior, and immunity · 2025Article
- Targeting the Kynurenine Pathway: A Novel Approach in Tumor Therapy.Expert reviews in molecular medicine · 2025Review
- Membrane Localization and Phosphorylation of Indoleamine 2,3-Dioxygenase 2 (IDO2) in A549 Human Lung Adenocarcinoma Cells: First Steps in Exploring Its Signaling Function.International journal of molecular sciences · 2023Article
- IL4i1 and IDO1: Oxidases that control a tryptophan metabolic nexus in cancer.The Journal of biological chemistry · 2023Review
- Review
- Article
- Absence of indoleamine 2,3‑dioxygenase 2 promotes liver regeneration after partial hepatectomy in mice.Molecular medicine reports · 2023Article
- The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer.Frontiers in oncology · 2023Review
- IDO1 and inflammatory neovascularization: bringing new blood to tumor-promoting inflammation.Frontiers in oncology · 2023Review
- The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.Frontiers in immunology · 2023Article
- Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia.Biomedicines · 2022Review
- An integrated cytokine and kynurenine network as the basis of neuroimmune communication.Frontiers in neuroscience · 2022Review
- Modulation of immune cell function, IDO expression and kynurenine production by the quorum sensor 2-heptyl-3-hydroxy-4-quinolone (PQS).Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
IDO2 is one of two closely related tryptophan catabolizing enzymes induced under inflammatory conditions. In contrast to the immunoregulatory role defined for IDO1 in cancer models, IDO2 has a proinflammatory function in models of autoimmunity and contact hypersensitivity. In humans, two common single-nucleotide polymorphisms have been identified that severely impair IDO2 enzymatic function, such that <25% of individuals express IDO2 with full catalytic potential. This, together with IDO2's relatively weak enzymatic activity, suggests that IDO2 may have a role outside of its function in tryptophan catabolism. To determine whether the enzymatic activity of IDO2 is required for its proinflammatory function, we used newly generated catalytically inactive IDO2 knock-in mice together with established models of contact hypersensitivity and autoimmune arthritis. Contact hypersensitivity was attenuated in catalytically inactive IDO2 knock-in mice. In contrast, induction of autoimmune arthritis was unaffected by the absence of IDO2 enzymatic activity. In pursuing this nonenzymatic IDO2 function, we identified GAPDH, Runx1, RANbp10, and Mgea5 as IDO2-binding proteins that do not interact with IDO1, implicating them as potential mediators of IDO2-specific function. Taken together, our findings identify a novel function for IDO2, independent of its tryptophan catabolizing activity, and suggest that this nonenzymatic function could involve multiple signaling pathways. These data show that the enzymatic activity of IDO2 is required only for some inflammatory immune responses and provide, to our knowledge, the first evidence of a nonenzymatic role for IDO2 in mediating autoimmune disease.
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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.