Summary of Study ST001241

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000830. The data can be accessed directly via it's Project DOI: 10.21228/M8D68Q This work is supported by NIH grant, U2C- DK119886.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001241
Study TitleGlobal Metabolic Analysis Trisomy 21 - Cohort 3, Plasma
Study SummaryGlobal metabolic analysis of plasma from individuals with and without trisomy 21.
University of Colorado Denver
Last NameCulp-Hill
First NameRachel
Address12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
Submit Date2019-08-13
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2019-08-21
Release Version1
Rachel Culp-Hill Rachel Culp-Hill application/zip

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Project ID:PR000830
Project DOI:doi: 10.21228/M8D68Q
Project Title:Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors
Project Summary:Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by unknown mechanisms. We report here a large metabolomics study of plasma and cerebrospinal fluid showing that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. We demonstrate that 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, we show positive correlations among levels of IFN-inducible cytokines and KP dysregulation. Using metabolic tracing assays, we determine that IFN stimulation causes IDO1 overexpression and kynurenine overproduction in cells with T21, dependent on overexpression of IFN receptors encoded on chromosome 21. Finally, we show a mouse model of DS carrying triplication of the IFN receptors exhibits KP dysregulation. Altogether, these results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS.
Institute:University of Colorado Denver
Laboratory:Linda Crnic Institute, Costello Lab, D'Alessandro Lab
Last Name:Culp-Hill
First Name:Rachel
Address:12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA