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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 OpenAlexfundno aff
Ubaid Ullah, Syed Bilal Ahmad Andrabi, Subhash Tripathi, Obaiah Dirasantha, Kartiek Kanduri, Sini Rautio, Catharina C. Groß, Sari Lehtimäki, Kanchan Bala, Johanna E. E. Tuomisto, Urvashi Bhatia, Deepankar Chakroborty, Laura L. Elo, Harri Lähdesmäki, Heinz Wiendl, Omid Rasool, Riitta Lahesmaa

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.

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 score0.002
Threshold uncertainty score0.006

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)0.0020.000

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

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

Citations71
Published2018
Admission routes1
Has abstractyes

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