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Record W4410698444 · doi:10.1016/j.ajt.2025.05.023

Cell therapy with human interleukin 10–producing ILC2s enhances islet function and inhibits allograft rejection

2025· article· en· W4410698444 on OpenAlexafffund
Sarah J. Colpitts, Sinthuja Jegatheeswaran, Amanda Oakie, Siavash Mashhouri, Nadia Sachewsky, Humaira Murshed, Jessica A. Mathews, Kyle T Reid, Paraish S. Misra, Vivian Fung, Trevor Reichman, M. Cristina Nostro, C. Bruce Verchere, Megan K. Levings, Sarah Q. Crome

Bibliographic record

VenueAmerican Journal of Transplantation · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicIL-33, ST2, and ILC Pathways
Canadian institutionsBC Children's HospitalToronto Rehabilitation InstituteToronto General HospitalStem Cell NetworkUniversity Health Network
FundersBanting and Best Diabetes Centre, University of TorontoCanadian Institutes of Health ResearchNovo NordiskCanada Foundation for InnovationCanadian Society of TransplantationCanada First Research Excellence FundCanada Research ChairsJuvenile Diabetes Research Foundation CanadaLeona M. and Harry B. Helmsley Charitable TrustNatural Sciences and Engineering Research Council of CanadaDiabetes CanadaEli Lilly CanadaBC Children's HospitalEli Lilly and Company
KeywordsMedicineIsletImmunologyFunction (biology)Cell therapyCellDiabetes mellitusCell biologyEndocrinologyBiochemistryBiology

Abstract

fetched live from OpenAlex

Group 2 innate lymphoid cells (ILC2s) that produce IL-10 (IL-10 + ILC2s) have demonstrated regulatory and tissue-protective properties in murine studies, but preclinical studies are lacking that explore the potential of human IL-10 + ILC2s as a tolerance-promoting cell therapy for transplantation or autoimmunity. Here, we investigated whether human IL-10 + ILC2s could enhance islet function and prevent allograft rejection in humanized mouse models of islet transplantation. In vitro , human IL-10 + ILC2s did not display cytotoxicity towards allogeneic deceased-donor islets or stem cell-derived islet-like cells, and co-transplantation with IL-10 + ILC2s significantly improved glucose control post-transplantation. Allogeneic IL10 + ILC2s directly inhibited T cell-mediated cytotoxicity against islet-like cells in vitro, and in an antigen-specific transplant rejection model, prevented T cell-mediated rejection of deceased donor islet grafts. Effects were greater with allogeneic IL-10 + ILC2s, as autologous cells did not inhibit T cell IFN-γ production or cytotoxic activity in vitro, and were not sufficient to prevent islet rejection in vivo. Collectively, these studies provide proof-of-principle that human IL-10 + ILC2s have therapeutic potential for islet transplantation and type 1 diabetes, and support their use as an allogeneic regulatory cell therapy.

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)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.002
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 head0.005
GPT teacher head0.220
Teacher spread0.214 · 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

Citations3
Published2025
Admission routes2
Has abstractno

Explore more

Same venueAmerican Journal of TransplantationSame topicIL-33, ST2, and ILC PathwaysFrench-language works237,207