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 |
Combined analysis:
Analysis ID | AN000313 |
---|---|
Analysis type | MS |
Chromatography type | Reversed phase |
Chromatography system | Agilent 1200 |
Column | Waters Acquity HSS T3 (50 x 2.1mm,1.8um) |
MS Type | ESI |
MS instrument type | Triple quadrupole |
MS instrument name | Agilent 6490 QQQ |
Ion Mode | POSITIVE |
Units | pmol/100 µg protein |
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 |
MS:
MS ID: | MS000262 |
Analysis ID: | AN000313 |
Instrument Name: | Agilent 6490 QQQ |
Instrument Type: | Triple quadrupole |
MS Type: | ESI |
Ion Mode: | POSITIVE |
Acquisition Parameters File: | QM-004-Xbridg2mm_ACar+_MRM-Insert.m.zip |
Processing Parameters File: | EX00317-acyl-carnitines-quant.m.zip |