ArticleNature communications2019
Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.
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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
96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 143 citations in OpenAlex.
- Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome.Molecular medicine (Cambridge, Mass.) · 2020Pooled it
- Trial
- Stored RBC metabolism as a function of caffeine levels.Transfusion · 2020Trial
- Trial
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Clinical considerations for immune dysregulation and immunodeficiency in Down syndrome.Journal of human immunity · 2026Review
- Metabolomic Profiles in Down Syndrome: A Scoping Review of Convergent and Context-Dependent Patterns.Journal of intellectual disability research : JIDR · 2026Article
- Immune dysregulation in children with Down syndrome: clinical implications and emerging therapies.Current opinion in rheumatology · 2026Review
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.eLife · 2026Article
- A mathematical model of folate-mediated one-carbon metabolism in Down syndrome.NPJ systems biology and applications · 2026Article
- An AI-Powered Trisomy 21 Research Assistant.bioRxiv : the preprint server for biology · 2026Article
- Systematic multi-omic deconvolution of the clinical heterogeneity of Down syndrome.Nature communications · 2026Article
- Long-Distance Trail Running Induces Inflammatory-Associated Protein, Lipid, and Purine Oxidation in Red Blood Cells.Blood red cells & iron · 2026Article
- Intracerebral age-independent reduction of endothelium-dependent hyperpolarization and nitric oxide signalling in the Dp16 mouse model of Down syndrome.The Journal of physiology · 2026Article
- Altered hepatic metabolism in Down syndrome.Cell reports · 2026Article
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.bioRxiv : the preprint server for biology · 2026Article
- Immunosuppression in down syndrome regression disorder: a prospective observational cohort study.Brain communications · 2026Article
- Telomere Biology, Erosion, and Age-Related Conditions: Insights from Down Syndrome and Other Telomere-Associated Disorders.Molecular neurobiology · 2025Review
- Down Syndrome Alters Type III IFN and Proinflammatory Airway Epithelial Responses to Respiratory Syncytial Virus Infection.American journal of respiratory cell and molecular biology · 2025Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma and cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. Immune cells of people with DS overexpress IDO1, the rate-limiting enzyme in the kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. Furthermore, the levels of IFN-inducible cytokines positively correlate with KP dysregulation. Using metabolic tracing assays, we show that overexpression of IFN receptors encoded on chromosome 21 contribute to enhanced IFN stimulation, thereby causing IDO1 overexpression and kynurenine overproduction in cells with T21. Finally, a mouse model of DS carrying triplication of IFN receptors exhibits KP dysregulation. Together, our results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS.
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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.