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Record W4405743098 · doi:10.1016/j.celrep.2024.115102

Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses

2024· article· en· W4405743098 on OpenAlexafffund
Kyle T Reid, Sarah J. Colpitts, Jessica A. Mathews, Abel Santos Carreira, Julia Murphy, Dorota Borovsky, Sinthuja Jegatheeswaran, Wenhui Cui, Tommy Alfaro Moya, Nadia Sachewsky, James An, Yubing Xia, Arthur Mortha, Jong Bok Lee, Zhang Li, Igor Novitzky‐Basso, Jonas Mattsson, Sarah Q. Crome

Bibliographic record

VenueCell Reports · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicIL-33, ST2, and ILC Pathways
Canadian institutionsUniversity of TorontoPrincess Margaret Cancer CentreUniversity Health Network
FundersCanadian Institutes of Health ResearchCanada First Research Excellence FundCanada Excellence Research Chairs, Government of CanadaCanada Foundation for InnovationCanadian Blood ServicesNatural Sciences and Engineering Research Council of CanadaToronto General and Western Hospital Foundation
KeywordsCellGraft-versus-host diseaseCell therapyDiseaseImmunologyT cellBiologyMedicineImmune systemGeneticsPathology

Abstract

fetched live from OpenAlex

Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2 10 ) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 10 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 10 conferred superior protection from GVHD than IL-10 −/low ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 10 protective effects, indicating that these cytokines are important for the protective effects of ILC2 10 . Notably, ILC2 10 provided comparable protection from GVHD to regulatory T cells without impairing T cell engraftment, instead decreasing intestinal T cell infiltration and suppressing CD4 + Th1 and CD8 + Tc1 cells. CITE-seq of expanded ILC2s revealed CD49d and CD86 are markers that allow for enrichment of ILC2 10 from conventional ILC2s and tracking of ILC2 10 in patient studies. Altogether, these findings demonstrate the potential of ILC2 10 in cell therapies for GVHD and other immune-mediated diseases.

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 categoriesMeta-epidemiology (narrow)
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 score0.192
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
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 head0.020
GPT teacher head0.238
Teacher spread0.218 · 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.

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

Citations9
Published2024
Admission routes2
Has abstractyes

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