Summary of project PR000830
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| 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 |
| Email: | rachel.hill@cuanschutz.edu |
| Phone: | 303-724-5798 |
Summary of all studies in project PR000830
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001240 | Global Metabolic Analysis Trisomy 21 - Cohort 2 | Homo sapiens | University of Colorado Denver | MS | 2019-08-21 | 1 | 194 | Uploaded data (8.6G)* |
| ST001241 | Global Metabolic Analysis Trisomy 21 - Cohort 3, Plasma | Homo sapiens | University of Colorado Denver | MS | 2019-08-21 | 1 | 258 | Uploaded data (6.6G)* |
| ST001242 | Global Metabolic Analysis Trisomy 21 - Cohort 3, CSF | Homo sapiens | University of Colorado Denver | MS | 2019-08-21 | 1 | 200 | Uploaded data (5G)* |
| ST001243 | Global Metabolic Analysis Trisomy 21 - Cohort 1 | Homo sapiens | University of Colorado Denver | MS | 2019-08-21 | 1 | 196 | Uploaded data (7.9G)* |
