ArticleScientific reports2017
Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- IDO family: the metabolic crossroads connecting immunity, nerves and tumors.Journal of translational medicine · 2026Review
- Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration.Nature communications · 2025Article
- Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK.Molecular metabolism · 2025Article
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dysregulated tryptophan metabolism: driving T cell subsets and PI3K-Akt pathway alterations in Hashimoto's thyroiditis.Frontiers in immunology · 2025Article
- Serum indoleamine 2, 3-dioxygenase and tryptophan-2, 3-dioxygenase: potential biomarkers for the diagnosis of major depressive disorder.Psychopharmacology · 2024Article
- Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15.Nature communications · 2023Article
- Monitoring Cultured Rat Hepatocytes Using RNA-Seq In Vitro.International journal of molecular sciences · 2023Article
- Effects of Ozone on Sickness and Depressive-like Behavioral and Biochemical Phenotypes and Their Regulation by Serum Amyloid A in Mice.International journal of molecular sciences · 2023Article
- Melatonin ameliorates disease severity in a mouse model of multiple sclerosis by modulating the kynurenine pathway.Scientific reports · 2022Article
- Article
- A comprehensive analysis of TDO2 expression in immune cells and characterization of immune cell phenotype in TDO2 knockout mice.Transgenic research · 2021Article
- The Aryl Hydrocarbon Receptor-Dependent TGF-α/VEGF-B Ratio Correlates With Disease Subtype and Prognosis in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
- Neurodegeneration in Multiple Sclerosis: Symptoms of Silent Progression, Biomarkers and Neuroprotective Therapy-Kynurenines Are Important Players.Molecules (Basel, Switzerland) · 2021Review
- Hypoxia Routes Tryptophan Homeostasis Towards Increased Tryptamine Production.Frontiers in immunology · 2021Article
- Hepatocyte-intrinsic type I interferon signaling reprograms metabolism and reveals a novel compensatory mechanism of the tryptophan-kynurenine pathway in viral hepatitis.PLoS pathogens · 2020Article
- Review
- Positive allosteric modulation of indoleamine 2,3-dioxygenase 1 restrains neuroinflammation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Intestinal Dysbiosis and Tryptophan Metabolism in Autoimmunity.Frontiers in immunology · 2020Review
- The therapeutic potential of targeting tryptophan catabolism in cancer.British journal of cancer · 2020Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system. TDO-deficiency is neuroprotective in C. elegans and Drosophila by increasing tryptophan and specific kynurenines. Here we have determined the role of TDO in autoimmunity and neurodegeneration in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We created reporter-TDO mice for in vivo imaging to show that hepatic but not CNS TDO expression is activated during EAE. TDO deficiency did not influence myelin-specific T cells, leukocyte infiltration into the CNS, demyelination and disease activity. TDO-deficiency protected from neuronal loss in the spinal cord but not in the optic nerves. While this protection did not translate to an improved overt clinical outcome, our data suggest that spatially distinct neuroprotection is conserved in mammals and support TDO as a potential target for treatment of diseases associated with neurodegeneration.
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