PXD056453-1

PXD056453 is an original dataset announced via ProteomeXchange.

Title	Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control
Description	Glucose is essential for T cell proliferation and function, yet the metabolic fates of glucose critical for T cell responses in vivo remain poorly defined. Here, we identify glycosphingolipid (GSL) biosynthesis as an essential arm of glucose metabolism that fuels CD8+ T cell expansion and cytotoxic function in vivo. Using stable isotope tracing, we show that CD8+ effector T (Teff) cells in vivo use glucose to synthesize uridine diphosphate-glucose (UDP-Glc), a common precursor for glycogen, glycan, and GSL biosynthesis. Blocking GSL production–by targeting the enzymes UDP-Glc pyrophosphorylase 2 (UGP2) or UDP-Glc ceramide glucosyltransferase (UGCG)–blunts CD8+ T cell expansion and cytotoxic activity without impacting glucose-dependent energy production. Mechanistically, we show that glucose-dependent GSL biosynthesis (via UGCG) maintains lipid integrity at the plasma membrane and is required for lipid raft aggregation following T cell receptor (TCR) stimulation. CD8+ T cells lacking UGCG display poor cytotoxic function and reduced tumor control in vivo. Together, our data highlight GSL biosynthesis as an essential metabolic fate for glucose–independent of energy production–required to maintain membrane lipid homeostasis and CD8+ T cell cytotoxic function in vivo.
HostingRepository	PRIDE
AnnounceDate	2025-08-08
AnnouncementXML	Submission_2025-08-08_00:40:26.350.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hyoungjoo Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-02 08:05:54	ID requested
⏵ 1	2025-08-08 00:40:26	announced

Dataset with its publication pending

submitter keyword: CD8+ T cells, Glycosphingolipid metabolism, UGCG, UDP-Glc

Russell Jones
contact affiliation	Chair, Department of Metabolism and Nutritional Programming Van Andel Institute
contact email	russell.jones@vai.org
lab head
Hyoungjoo Lee
contact affiliation	Van Andel Institute
contact email	hyoungjoo.lee@vai.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056453
     1. Label: PRIDE project
     2. Name: Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control