Summary of Study ST000211
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 PR000153. The data can be accessed directly via it's Project DOI: 10.21228/M8B01C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST000211 |
| Study Title | T cell metabolism during graft-versus-host disease (CAB 307)-PART II |
| Study Type | Acyl-carnitine analysis (plasma) |
| Study Summary | The coinhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity of graft-versus-host disease (GVHD), but the interplay between PD-1 inhibition and T cell metabolism is not well studied. We found that both murine and human alloreactive T cells concomitantly upregulated PD-1 expression and increased levels of reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1HiROSHi phenotype was specific to alloreactive T cells and was not observed in syngeneic T cells during homeostatic proliferation. Blockade of PD-1 signaling decreased both mitochondrial H2O2 and total cellular ROS levels, and PD-1–driven increases in ROS were dependent upon the oxidation of fatty acids, because treatment with etomoxir nullified changes in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels impaired T cell survival in a process reversed by antioxidants. Furthermore, PD-1–driven changes in ROS were fundamental to establishing a cell’s susceptibility to subsequent metabolic inhibition, because blockade of PD-1 decreased the efficacy of later F1F0-ATP synthase modulation. These data indicate that PD-1 facilitates apoptosis in alloreactive T cells by increasing ROS in a process dependent upon the oxidation of fat. In addition, blockade of PD-1 undermines the potential for subsequent metabolic inhibition, an important consideration given the increasing use of anti–PD-1 therapies in the clinic. Research is published, core data not used but project description is relevant: http://www.jimmunol.org/content/194/12/5789.long |
| Institute | University of Michigan |
| Department | Biomedical Research Core Facilities |
| Laboratory | Metabolomics core |
| Last Name | Kachman |
| First Name | Maureen |
| Address | 6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714 |
| mkachman@umich.edu | |
| Submit Date | 2015-06-12 |
| Num Groups | 2 |
| Total Subjects | 7 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Uploaded File Size | 7 M |
| Analysis Type Detail | LC-MS |
| Release Date | 2015-12-28 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000153 |
| Project DOI: | doi: 10.21228/M8B01C |
| Project Title: | Graft-Versus-Host Disease |
| Project Summary: | T cell metabolism during graft-versus-host disease |
| Institute: | University of Michigan |
| Department: | Pediatrics |
| Laboratory: | Ferrara lab |
| Last Name: | Byersdorfer |
| First Name: | Craig |
| Address: | Ann Arbor, MI |
| Email: | craigbye@med.umich.edu |
| Phone: | 734-000-0000 |
Subject:
| Subject ID: | SU000230 |
| Subject Type: | Animal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA010422 | S00015099 | Control |
| SA010423 | S00015100 | Control |
| SA010424 | S00015098 | Control |
| SA010425 | S00015097 | Control |
| SA010426 | S00015095 | GVHD |
| SA010427 | S00015096 | GVHD |
| SA010428 | S00015094 | GVHD |
| Showing results 1 to 7 of 7 |
Collection:
| Collection ID: | CO000218 |
| Collection Summary: | - |
| Sample Type: | Cells |
Treatment:
| Treatment ID: | TR000238 |
Sample Preparation:
| Sampleprep ID: | SP000232 |
| Sampleprep Summary: | - |
| Sampleprep Protocol Filename: | Acyl-carnitines_analysis_protocol-CR-MK-20150528.docx |
Chromatography:
| Chromatography ID: | CH000234 |
| Methods ID: | AQM050 |
| Methods Filename: | QM-004-Xbridg2mm_ACar+_MRM-Insert.m.zip |
| Instrument Name: | Agilent 1200 |
| Column Name: | Waters Acquity HSS T3 (50 x 2.1mm,1.8um) |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN000313 |
| Laboratory Name: | MRC2 (University of Michigan) |
| Analysis Type: | MS |
| Acquisition ID: | AQM050 |
| Acquisition Parameters File: | QM-004-Xbridg2mm_ACar+_MRM-Insert.m.zip |
| Instrument Name: | Agilent QQQ 6490 |
| Processing Parameters File: | EX00317-acyl-carnitines-quant.m.zip |
| Chromatography ID: | CH000234 |
| Num Factors: | 2 |
| Num Metabolites: | 30 |
| Units: | pmol/100 µg protein |
