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 |
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Treatment:
Treatment ID: | TR000238 |