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ILC2 + DC = Th2, group 2 innate lymphoid cell derived IL-13 is essential for efficient T helper 2 cell differentiation in allergic lung inflammation. (HYP6P.258)

2014· article· en· W1516388861 on OpenAlexaff
Timotheus Y.F. Halim, Catherine A. Steer, Laura Mathä, Matthew Gold, Itziar Martínez-González, Kelly M. McNagny, Andrew N. J. McKenzie, Fumio Takei

Bibliographic record

VenueThe Journal of Immunology · 2014
Typearticle
Languageen
FieldImmunology and Microbiology
TopicIL-33, ST2, and ILC Pathways
Canadian institutionsArthritis Research Centre of CanadaTerry Fox Research InstituteUniversity of British Columbia
Fundersnot available
KeywordsInnate lymphoid cellImmunologyHoming (biology)Allergic inflammationAdoptive cell transferT cellInflammationChemokineBiologyImmune systemAcquired immune systemCell biology

Abstract

fetched live from OpenAlex

Abstract Naïve CD4+ T cell differentiation into distinct subsets of T helper (Th) cells is a pivotal process in the initiation of the adaptive immune response. Allergens predominantly stimulate Th2 cells, causing allergic inflammation. However, why allergens induce Th2 cell differentiation is not understood. Here we show that Group 2 Innate Lymphoid Cells (ILC2) are required to mount a robust Th2 cell response to the protease-allergen papain. Intranasal administration of papain stimulates ILC2 and Th2 cells, causing allergic lung inflammation and elevated IgE titre. This process is severely impaired in ILC2-deficient mice. More careful analysis reveals that ILC2 derived IL-13 is important for Th2 cell differentiation. Adoptive transplant of WT but not IL-13KO ILC2s restores the Th2 response. Recombinant IL-13 administration also rescues the Th2 defect in ILC2-deficient mice. Notably, intranasal IL-13 + OVA injection efficiently drives Th2 skewing of OTII transgenic T cells. Mechanistically, we show that IL-13 has a profound effect on homing of dendritic cells to the draining lymph-node, where they prime naïve CD4+ T cells. Lung explant from IL-13KO mice cultured in a transwell system show severely impaired DC migration to lymph-node homing chemokine gradients. Moreover, these processes require IL-33-dependent ILC2 activation, which suggests a common pathway in the initiation of the Th2 response to allergens.

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 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 score0.034
Threshold uncertainty score0.898

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
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 head0.005
GPT teacher head0.198
Teacher spread0.193 · 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 teacher head, 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

Citations0
Published2014
Admission routes1
Has abstractyes

Explore more

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