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Record W4386055115 · doi:10.1101/2023.08.21.554158

Cell therapy with IL-10-producing group 2 innate lymphoid cells suppresses Graft-versus-Host disease

2023· preprint· en· W4386055115 on OpenAlexafffund
Kyle T Reid, Sarah J. Colpitts, Jessica A. Mathews, Abel Santos Carreira, Julia Murphy, Dorota Borovsky, Wenhui Cui, Tommy Alfaro Moya, Nadia Sachewsky, James An, Yubing Xia, Arthur Mortha, Jong Bok Lee, Li Zhang, Igor Novitzky‐Basso, Jonas Mattsson, Sarah Q. Crome

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicIL-33, ST2, and ILC Pathways
Canadian institutionsPrincess Margaret Cancer CentreToronto General HospitalUniversity of TorontoUniversity Health Network
FundersCanada First Research Excellence FundNatural Sciences and Engineering Research Council of CanadaMitacsNovo NordiskCanadian Blood Services
KeywordsInnate lymphoid cellImmunologyAdoptive cell transferImmune systemNodCD8Graft-versus-host diseaseCD80BiologyCell therapyInnate immune systemCellStem cellCancer researchT cellMedicineCytotoxic T cellCell biologyIn vivoCD40

Abstract

fetched live from OpenAlex

Abstract IL-10 producing group 2 innate lymphoid cells (ILC2 10 ) have immunoregulatory functions, and limit harmful immune responses across various tissues. Despite their crucial roles in maintaining immune homeostasis, the cell therapy potential of human ILC2 10 has not been demonstrated, due to both limited numbers in human peripheral blood and lack of definitive markers for identification. Here, we isolate and expand circulating human ILC2 10 , and assess their cell therapy potential in a humanized model of Graft-versus-Host Disease (GVHD). Cell therapy with human ILC2 10 decreased GVHD severity and prolonged survival of NOD- scid IL2Rγ null (NSG) mice. Adoptive transfer of ILC2 10 inhibited pathogenic T cell proliferation and intestinal infiltration, and suppressed CD4 + Th1 and CD8 + Tc1 cells in an IL-4 and IL-10 dependent manner. Critically, increased proportions of ILC2s did not correlate with higher rates of cancer relapse in HSCT recipients, and adoptive transfer of ILC2 10 did not compromise graft-versus-leukemic (GVL) effects in a humanized model. Finally, we identify CD49d and CD86 as novel markers that discriminate ILC2 10 from conventional ILC2s. Collectively, these findings demonstrate the potential of harnessing ILC2 10 in cell therapies for GVHD and other immune-driven pathologies.

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), Insufficient 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 score0.130
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.002

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 head0.019
GPT teacher head0.206
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 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

Citations1
Published2023
Admission routes2
Has abstractyes

Explore more

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