PXD001789

PXD001789 is an original dataset announced via ProteomeXchange.

Title	Foxp3 positive and negative cell comparison
Description	Regulatory T cells 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 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. ATP was secreted by both T effector and regulatory T cells and was reduced by mitochondrial respiration inhibitors. Thus Foxp3 imparts a selective advantage in ATP generation capacity to the cell and may exploit this as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a comparative 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 T cells and Foxp3 positive iTreg and Foxp3 negative activated CD4 T cells in addition to human peripheral blood natural Treg. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 drives a significant up regulation of several members of the mitochondrial electron transport chain.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:22:56.021.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duncan Howie
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	6x(13)C labeled residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-02-06 08:27:46	ID requested
1	2017-02-15 11:36:11	announced
⏵ 2	2024-10-22 04:23:04	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: Biological, Biomedical

submitter keyword: mouse T cells

Dr Duncan Howie
contact affiliation	Oxford University Sir William Dunn School of Pathology, Oxford, OX1 3RE, UK
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/PXD001789

PRIDE project URI

• PRIDE
  1. PXD001789
     1. Label: PRIDE project
     2. Name: Foxp3 positive and negative cell comparison