PXD001906

PXD001906 is an original dataset announced via ProteomeXchange.

Title	Human Treg LC-MSMS - Foxp3 drives oxidative phosphorylation and protection from lipotoxicity
Description	Regulatory T cells (Treg) have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to meet increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and, in addition, the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. Foxp3 also imparts a selective advantage in ATP generation capacity, one that might be exploited as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing CD4+ T cells from various sources with Foxp3- activated CD4 T cells, as well as Treg from human peripheral blood. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 expression is associated with a significant up regulation of several members of the mitochondrial electron transport chain. Not only does Foxp3 influence genes directly concerned with immune function, but also with the energy generating functions of Treg.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:23:15.133.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duncan Howie
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-03-12 02:29:03	ID requested
1	2017-02-15 12:06:05	announced
⏵ 2	2024-10-22 04:23:18	announced	2024-10-22: Updated project metadata.

Howie D, Cobbold SP, Adams E, Ten Bokum A, Necula AS, Zhang W, Huang H, Roberts DJ, Thomas B, Hester SS, Vaux DJ, Betz AG, Waldmann H, Foxp3 drives oxidative phosphorylation and protection from lipotoxicity. JCI Insight, 2(3):e89160(2017) [pubmed]

10.1172/jci.insight.89160;

curator keyword: Biomedical

submitter keyword: Human T cell Treg Foxp3 LC-MSMS

Duncan Howie
contact affiliation	Oxford University, Sir William Dunn School of Pathology, Oxford
contact email	duncan.howie@path.ox.ac.uk
lab head
Duncan Howie
contact affiliation	Oxford University
contact email	duncan.howie@path.ox.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/02/PXD001906

PRIDE project URI

• PRIDE
  1. PXD001906
     1. Label: PRIDE project
     2. Name: Human Treg LC-MSMS - Foxp3 drives oxidative phosphorylation and protection from lipotoxicity