PXD068522-1

PXD068522 is an original dataset announced via ProteomeXchange.

Title	Sialoglycans on human T cells attenuate death programs executed through the Fas pathway
Description	T cells are critical executors of adaptive immune functions and their persistence is tightly regulated. Part of this regulation relies on programmed cell death driven by the Tumour Necrosis Factor (TNF) receptor superfamily. The addition of glycans that terminate in the monosaccharide sialic acid (sialoglycans) to these cell death receptors has been shown to attenuate their apoptotic functions. While this is now understood to be a pro-survival mechanism in settings of cancer pathophysiology, the specific roles of sialoglycans in regulating cell death receptor activity on human T cells remains unexplored. This of particular importance given the rising interest in glycan editing of T cells for therapeutic benefit. Here, we address this gap using both immortalized (Jurkat) and primary human T cells deficient in sialoglycans. We found that T cell sialoglycans suppressed apoptosis induced by the Fas receptor (FasR) but not other TNF receptor superfamily members such as TNFR1 and TRAIL-RI. Dynamic reorganization of FasR was increased on sialoglycan deficient Jurkat cells, suggesting that these glycans limit receptor clustering. This model was further supported by phosphoproteomics results, which confirmed that loss of sialoglycans negatively regulated the pro-survival MAPK/ERK signalling pathway. Finally, we used a recombinant sialic acid cleaving enzyme (sialidase) to confirm that sialoglycans on primary human T cells are bona fide immunophysiological regulators of FasR-driven apoptosis. Combined, our results demonstrate that sialoglycan remodelling on T cells influences cell fate driven by the Fas pathway and provide motivation to further characterize the immunoregulatory roles of the glycocalyx in health and disease.
HostingRepository	PRIDE
AnnounceDate	2025-12-30
AnnouncementXML	Submission_2025-12-30_08:11:04.428.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Emmajay Sutherland
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-19 01:20:03	ID requested
⏵ 1	2025-12-30 08:11:05	announced

10.1016/j.jbc.2025.111047;

Affe V, Lei Q, Veth TS, Sutherland E, Choksi H, Izzati FN, Shi Q, Cui H, Riley NM, Edgar LJ, Sialoglycans on human T cells attenuate death programs executed through the Fas pathway. J Biol Chem, 302(2):111047(2025) [pubmed]

submitter keyword: immunology, glycobiology, sialic acid, apoptosis,T cells

Landon J. Edgar
contact affiliation	Department of Pharmacology & Toxicology 1 King’s College Circle Toronto, ON, Canada, M5S 1A8
contact email	landon.edgar@utoronto.ca
lab head
Emmajay Sutherland
contact affiliation	University of Washington
contact email	emmajay.sutherland@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068522
     1. Label: PRIDE project
     2. Name: Sialoglycans on human T cells attenuate death programs executed through the Fas pathway