PXD036292-1

PXD036292 is an original dataset announced via ProteomeXchange.

Title	Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation
Description	Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. However, the metabolic pathways critical for optimal T cell responses remain poorly understood. Here, we identify ketone bodies (KBs) – including -hydroxybutyrate (OHB) and acetoacetate (AcAc) – as essential fuels supporting CD8+ T cell metabolism and effector function. Ketolysis is an intrinsic feature of highly functional CD8+ T effector (Teff) cells and OHB directly increases CD8+ Teff cell IFN- production and cytolytic activity. Using metabolic tracers, we establish that CD8+ Teff cells preferentially use KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boost the respiratory capacity of CD8+ T cells and TCA cycle-dependent metabolic pathways that fuel T cell growth. Mechanistically, we find that OHB is a major substrate for acetyl-CoA production in CD8+ T cells and regulates effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.
HostingRepository	PRIDE
AnnounceDate	2023-10-11
AnnouncementXML	Submission_2023-10-11_09:17:05.415.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	DominiqueLevesque
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	autoflex

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-25 14:31:38	ID requested
⏵ 1	2023-10-11 09:17:05	announced
2	2023-11-14 07:12:28	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:05:38	announced	2024-10-22: Updated project metadata.

submitter keyword: histone,ketolysis, acetylation, mass spectrometry, CD8+

Russel GJones
contact affiliation	Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA
contact email	russell.jones@vai.org
lab head
DominiqueLevesque
contact affiliation	University of Sherbrooke, FM Boisvert lab
contact email	dominique.levesque@usherbrooke.ca
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/2023/10/PXD036292

PRIDE project URI

• PRIDE
  1. PXD036292
     1. Label: PRIDE project
     2. Name: Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation