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Record W4322489142 · doi:10.1101/2023.02.26.529772

FOXP3 <sup>+</sup> regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues

2023· preprint· en· W4322489142 on OpenAlexaff
Hunter A. Martinez, Ievgen Koliesnik, Gernot Kaber, Jacqueline Kelsey Reid, Nadine Nagy, Graham L. Barlow, Ben Falk, Carlos Medina, Aviv Hargil, Israël Vlodavsky, Jin‐Ping Li, Magdiel Pérez-Cruz, Sai-Wen Tang, Everett Meyer, Lucile E. Wrenshall, James D. Lord, K. Christopher García, Theo D. Palmer, Lawrence Steinman, Gerald T. Nepom, Thomas N. Wight, Paul L. Bollyky, Hedwich F. Kuipers

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProteoglycans and glycosaminoglycans research
Canadian institutionsUniversity of Calgary
FundersNational Institutes of HealthLeona M. and Harry B. Helmsley Charitable Trust
KeywordsHeparanaseFOXP3Cell biologyChemistryMolecular biologyBusinessImmunologyBiologyCellBiochemistryImmune system

Abstract

fetched live from OpenAlex

Abstract FOXP3 + regulatory T cells (Treg) depend on exogenous IL-2 for their survival and function, but circulating levels of IL-2 are low, making it unclear how Treg access this critical resource in vivo . Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE -/- Treg have impaired stability and function in vivo , including the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their tolerogenic function in vivo . Together, these data identify novel roles for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity. One-Sentence Summary Regulatory T cells use heparanase to strip IL-2 bound to extracellular matrix within inflamed tissues, thereby supporting their homeostasis and function.

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 score0.013
Threshold uncertainty score0.042

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0130.005

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 head0.030
GPT teacher head0.286
Teacher spread0.256 · 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

Citations2
Published2023
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicProteoglycans and glycosaminoglycans researchFrench-language works237,207