MétaCan
Menu
← Back to cohort
Record W4405183426 · doi:10.1101/2024.12.06.627213

Age-related remodeling of the glycocalyx drives T cell exhaustion

2024· preprint· en· W4405183426 on OpenAlexaff
Hanlin Zhang, C. Kimberly Tsui, Jesse Garcia Castillo, Andrea Evangelista, Esther Jeong Yoon Kim, Larry Joe, Nicholas Twells, Ellen A. Robey, Lara K. Mahal, Michel DuPage, Andrew Dillin

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGlycosylation and Glycoproteins Research
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsGlycocalyxSialic acidImmune systemGlycanCell biologyCellT cellDownregulation and upregulationBiologyImmunologyBiochemistryGeneGlycoprotein

Abstract

fetched live from OpenAlex

Abstract Cell surface glycans, termed the glycocalyx, are essential regulators of cellular signaling and thus cellular development and functions, but how aging impacts the glycocalyx remains poorly understood. Here, using immune cells as a model system for studying the relationship between aging and glycocalyx remodeling, we show that α2,6-linked sialic acid – a terminal glycan epitope typically associated with inhibitory signaling – becomes downregulated in T cells from older animals. This downregulation is tightly correlated with age-associated accumulation of effector T cells, which are decorated with little to no α2,6-linked sialic acids. T cell aging renders older individuals more vulnerable to infections and cancers. To understand the role of α2,6-linked sialic acids in T cell physiology, we generated a mouse model with T cell-specific deletion of the sialyltransferase gene St6gal1 . The chronic depletion of α2,6-linked sialic acids led to naïve T (T N ) cells expansion in the periphery and premature T cell exhaustion. As a result, these mice were less able to control acute Listeria infection and chronic tumor growth. Blockade of the PD-1 pathway can partially restore the ability of St6gal1 -deficient T cells to control tumor growth. Together, these data suggest that α2,6-linked sialic acids are critical for maintaining long-term T cell responsiveness, and the loss of α2,6-linked sialic acids may directly contribute to age-related T cell exhaustion.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.234
Teacher spread0.223 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGlycosylation and Glycoproteins Research→French-language works237,207→