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Record W2948717154 · doi:10.1101/658542

The neonatal microenvironment programs conventional and intestinal Tbet <sup>+</sup> γδT17 cells through the transcription factor STAT5

2019· preprint· en· W2948717154 on OpenAlexaff
Darshana Kadekar, Rasmus Agerholm, John Rizk, Heidi A. Neubauer, Tobias Suske, Barbara Maurer, Mònica Torrellas Viñals, Elena M. Comelli, Amel Taïbi, Richard Moriggl, Vasileios Bekiaris

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsUniversity of Toronto
FundersLundbeckfondenH. Lundbeck A/SNational Institutes of HealthNational Institute of Arthritis and Musculoskeletal and Skin DiseasesLEO FondetAustrian Science Fund
KeywordsBiologyAutoimmunityRAR-related orphan receptor gammaExperimental autoimmune encephalomyelitisSTAT3Transcription factorImmune systemEmbryonic stem cellCell biologyImmunologyCancer researchFOXP3Signal transductionBiochemistry

Abstract

fetched live from OpenAlex

Summary Interleukin(IL)-17-producing RORγt + γδ T (γδT17) cells develop in the embryonic thymus and participate in type 3 immune responses. Herein we show that γδT17 cells rapidly proliferate within neonatal lymph nodes and gut, where upon entry they uniquely upregulate Tbet and co-express IL-17, IL-22 and interferon(IFN) γ in a STAT3 and retinoic acid dependent manner. Neonatal expansion was halted in mice conditionally deficient in STAT5 and its loss resulted in γδT17 cell depletion from all adult organs. Hyperactive STAT5 mutant mice showed that the STAT5A homologue had a dominant role over STAT5B in promoting γδT17 cell expansion and downregulating gut-associated Tbet. In contrast, STAT5B preferentially expanded IFNγ-producing γδ populations. Importantly, mice lacking γδT17 cells due to STAT5 deficiency displayed a profound resistance to experimental autoimmune encephalomyelitis. Our data identify for the first time STAT5 as a key molecular checkpoint allowing γδT17 cells to pass through a critical neonatal developmental window to acquire tissue-specific characteristics essential for infection and 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.

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 score0.003
Threshold uncertainty score0.011

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)0.0030.001

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 head0.198
Teacher spread0.187 · 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
Published2019
Admission routes1
Has abstractyes

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