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.

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Study IDST000211
Study TitleT cell metabolism during graft-versus-host disease (CAB 307)-PART II
Study TypeAcyl-carnitine analysis (plasma)
Study SummaryThe 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
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Email mkachman@umich.edu
Submit Date2015-06-12
Num Groups2
Total Subjects7
Raw Data AvailableYes
Raw Data File Type(s).xml,.xsd,.stg, .bin, .cd,.cG
Uploaded File Size7 M
Analysis Type DetailLC-MS
Release Date2015-12-28
Release Version1
Maureen Kachman Maureen Kachman
https://dx.doi.org/10.21228/M8B01C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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
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