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Record W4404020334 · doi:10.1038/s41467-024-51719-6

CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner

2024· article· en· W4404020334 on OpenAlexfundno aff
Jonathan W. Lo, Jan-Hendrik Schroeder, Luke B. Roberts, Rami Mohamed, Domenico Cozzetto, Gordon Beattie, Omer Omer, Ellen M. Ross, Frank Heuts, Geraldine M. Jowett, Emily Read, Matthew Madgwick, Joana F. Neves, Tamás Korcsmáros, Richard G. Jenner, Lucy S. K. Walker, Nick Powell, Graham M. Lord

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicIL-33, ST2, and ILC Pathways
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilMedical Research CouncilUniversity of TorontoWellcomeImperial College LondonSt. George's, University of LondonResearch Councils UKDepartment of Health and Social CareKing's College LondonUK Research and InnovationNational Institute for Health and Care ResearchSunnybrook Research InstituteCancer Research UKWellcome Trust
KeywordsInnate lymphoid cellBiologyImmunologyInnate immune systemMicrobiomeHomeostasisInflammatory bowel diseaseGut floraImmune systemPopulationInflammationAcquired immune systemImmunityCell biologyCTLA-4DiseaseT cellMedicineGenetics

Abstract

fetched live from OpenAlex

The maintenance of intestinal homeostasis is a fundamental process critical for organismal integrity. Sitting at the interface of the gut microbiome and mucosal immunity, adaptive and innate lymphoid populations regulate the balance between commensal micro-organisms and pathogens. Checkpoint inhibitors, particularly those targeting the CTLA-4 pathway, disrupt this fine balance and can lead to inflammatory bowel disease and immune checkpoint colitis. Here, we show that CTLA-4 is expressed by innate lymphoid cells and that its expression is regulated by ILC subset-specific cytokine cues in a microbiota-dependent manner. Genetic deletion or antibody blockade of CTLA-4 in multiple in vivo models of colitis demonstrates that this pathway plays a key role in intestinal homeostasis. Lastly, we have found that this observation is conserved in human IBD. We propose that this population of CTLA-4-positive ILC may serve as an important target for the treatment of idiopathic and iatrogenic intestinal inflammation.

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)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.670
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0000.001

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 head0.016
GPT teacher head0.268
Teacher spread0.252 · 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

Citations16
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicIL-33, ST2, and ILC PathwaysFrench-language works237,207