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Record W2787958089 · doi:10.1016/j.celrep.2018.01.070

Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

2018· article· en· W2787958089 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.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueCell Reports · 2018
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsnot available
FundersEuropean Research CouncilTurun Yliopistollinen KeskussairaalaVarsinais-Suomen SairaanhoitopiiriBiocenter FinlandInterdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum WürzburgSigrid Juséliuksen SäätiöTurun YliopistoSweden-Japan FoundationGemeinnützige Hertie-StiftungTekesBiogenCalifornia Department of Fish and GameElse Kröner-Fresenius-StiftungJuvenile Diabetes Research Foundation AustraliaEuropean CommissionÅbo AkademiJuvenile Diabetes Research Foundation United KingdomJuvenile Diabetes Research Foundation InternationalAmerican Osteopathic FoundationBC Children’s Hospital FoundationBundesministerium für Bildung und ForschungPaulon SäätiöCanadian Institute of Mining, Metallurgy and PetroleumDeutsche ForschungsgemeinschaftGlaxoSmithKlineAcademy of Finland
KeywordsEffectorFOXP3BiologyImmune systemTranscription factorRepressorIn vitroCell biologyDownregulation and upregulationTranscriptional regulationGeneRegulation of gene expressionFunction (biology)Cancer researchImmunologyGenetics

Abstract

fetched live from OpenAlex

Regulatory T (Treg) cells are critical in regulating the immune response. In vitro induced Treg (iTreg) cells have significant potential in clinical medicine. However, applying iTreg cells as therapeutics is complicated by the poor stability of human iTreg cells and their variable suppressive activity. Therefore, it is important to understand the molecular mechanisms of human iTreg cell specification. We identified hypermethylated in cancer 1 (HIC1) as a transcription factor upregulated early during the differentiation of human iTreg cells. Although FOXP3 expression was unaffected, HIC1 deficiency led to a considerable loss of suppression by iTreg cells with a concomitant increase in the expression of effector T cell associated genes. SNPs linked to several immune-mediated disorders were enriched around HIC1 binding sites, and in vitro binding assays indicated that these SNPs may alter the binding of HIC1. Our results suggest that HIC1 is an important contributor to iTreg cell development 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.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
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 score0.095
Threshold uncertainty score0.997

Codex and Gemma teacher scores by category

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)0.0040.000

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 head0.014
GPT teacher head0.239
Teacher spread0.225 · 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