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Record W3137645650 · doi:10.1126/science.aaz4544

WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity

2021· article· en· W3137645650 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueScience · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsMcGill UniversityPrincess Margaret Cancer CentreUniversity of TorontoToronto General HospitalLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersCanadian Institutes of Health ResearchCanada Research Chairs
KeywordsPI3K/AKT/mTOR pathwayCell biologyAutoimmunityT cellBiologyActin cytoskeletonSignal transductionConditional gene knockoutCellCytoskeletonPhenotypeImmune systemImmunologyBiochemistryGene

Abstract

fetched live from OpenAlex

ablation in T cells causes severe autoimmunity associated with increased mammalian target of rapamycin (mTOR) activation and metabolic reprogramming that engender spontaneous activation and accelerated differentiation of peripheral T cells. These mice also manifest diminished antigen-specific T cell responses associated with increased inhibitory receptor expression, dysregulated mitochondrial function, and reduced cell survival upon activation. Mechanistically, WAVE2 directly bound mTOR and inhibited its activation by impeding mTOR interactions with RAPTOR (regulatory-associated protein of mTOR) and RICTOR (rapamycin-insensitive companion of mTOR). Both the T cell defects and immunodysregulatory disease were ameliorated by pharmacological mTOR inhibitors. Thus, WAVE2 restraint of mTOR activation is an absolute requirement for maintaining the T cell homeostasis supporting adaptive immune responses and preventing autoimmunity.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.048
Threshold uncertainty score0.555

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.008
GPT teacher head0.237
Teacher spread0.229 · 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