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Record W4405614588 · doi:10.1172/jci.insight.181481

MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn’s disease

2024· article· en· W4405614588 on OpenAlexafffund
Elena Layunta, Sofia Jäverfelt, Fleur C. van de Koolwijk, Molly Sivertsson, Brendan Dolan, Liisa Arike, Sara Thulin, Bruce A. Vallance, Thaher Pelaseyed

Bibliographic record

VenueJCI Insight · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsBC Children's HospitalUniversity of British Columbia
FundersSahlgrenska AkademinUppsala Multidisciplinary Center for Advanced Computational ScienceStiftelsen Clas Groschinskys MinnesfondJeanssons StiftelserGöteborgs UniversitetKnut och Alice Wallenbergs StiftelseSvenska Sällskapet för Medicinsk ForskningSahlgrenska UniversitetssjukhusetScience for Life LaboratoryVästra GötalandsregionenVetenskapsrådetNational Institute of Allergy and Infectious DiseasesStiftelserna Wilhelm och Martina LundgrensNational Institutes of HealthBiocodex Microbiota FoundationWenner-Gren StiftelsernaCH.I.L.D. FoundationÅke Wiberg Stiftelse
KeywordsMucinGlycocalyxIleumBiologyImmune systemSmall intestineCrohn's diseaseBacteriaInflammationMicrobiologyCryptCell biologyImmunologyDiseasePathologyMedicineBiochemistryGeneticsEndocrinology

Abstract

fetched live from OpenAlex

Crohn's disease (CD) is the chronic inflammation of the terminal ileum and colon triggered by a dysregulated immune response to bacteria, but insights into specific molecular perturbations at the critical bacteria-epithelium interface are limited. Here, we report that the membrane mucin MUC17 protected small intestinal enterocytes against commensal and pathogenic bacteria. In noninflamed CD ileum, reduced MUC17 levels and a compromised glycocalyx barrier allowed recurrent bacterial contact with enterocytes. Muc17 deletion in mice rendered the small intestine particularly prone to atypical bacterial infection while maintaining resistance to colitis. The loss of Muc17 resulted in spontaneous deterioration of epithelial homeostasis and in the extraintestinal translocation of bacteria. Finally, Muc17-deficient mice harbored specific small intestinal bacterial taxa observed in patients with CD. Our findings highlight MUC17 as an essential region-specific line of defense in the small intestine with relevance for early epithelial defects in CD.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.575
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
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.019
GPT teacher head0.262
Teacher spread0.243 · 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 designObservational
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

Citations12
Published2024
Admission routes2
Has abstractyes

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