Evidence map›Paper›PMID 41169355›Full record

ArticleFrontiers in immunology2025

Human colon stem cells are the predominant epithelial responders to bacterial antigens.

Maaike H De Vries, Claartje A Meddens, Hemme J Hijma, Anne-Claire Berrens, Suze A Jansen, Berend A P Kooiman, Scott Snapper, Hans Clevers, Michal Mokry, Ewart W Kuijk and 1 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Maaike H De VriesDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Claartje A MeddensDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Hemme J HijmaDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Anne-Claire BerrensDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Suze A JansenDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Berend A P KooimanDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Scott SnapperDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children's Hospital, Boston, MA, United States.
Hans CleversOncode Institute, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
Michal MokryDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Ewart W Kuijk *Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Edward E S Nieuwenhuis *Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.

Funding

Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel DiseaseRC2DK122532 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI KLEIN, CHRISTOPH, MUISE, ALEIXO M · 2020 to 2024
$9.1M
NIDDK NIH HHS RC2 DK122532
6 · The paper itself

Abstract

Intestinal epithelial cells (IECs) are capable of mounting an adequate antimicrobial inflammatory response to pathogens while tolerating commensals. The underlying regulatory mechanisms of immune sensitivity remain incompletely understood, particularly in the context of human IECs. To enhance our understanding of the immune response of IECs to bacterial epithelial barrier breach, we investigated whether epithelial responsiveness is contingent on cell identity and cell polarization. We exposed human intestinal organoids to bacterial antigens to study their immune responses. Notable discrepancies were observed in the specific reactions exhibited by intestinal stem cells (ISCs) and enterocytes. It was determined that basolateral exposure of IECs to bacterial antigens resulted in a robust response, whereas apical exposure elicited a significantly more modest response. We identified ISCs as the principal responders, while the reaction of enterocytes was found to be attenuated. The regulation of bacterial responsiveness in enterocytes occurs at multiple levels, including the modulation of NFκB activation and post-transcriptional control of mRNA stability. Our findings demonstrate that differentiated non-responsive enterocytes can be sensitized to bacterial antigens through the activation of the WNT pathway. These findings extend the crucial role of WNT signaling for intestinal epithelial homeostasis and regulation of stem cell maintenance, proliferation, differentiation, and tissue architecture in the gut. Additionally, they reveal a new function of WNT signaling in regulating microbial responses within the intestinal environment.

Indexed as

Antigens, BacterialColonEnterocytesEpithelial CellsIntestinal MucosaStem CellsCell DifferentiationHumansNF-kappa BOrganoidsWnt Signaling PathwayAntigens, BacterialNF-kappa Bimmune regulationinflammatory bowel diseaseinnate immunityintestinal epitheliumintestinal stem cellsWNT pathway

Identifiers

PMID41169355
PMCPMC12568582

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.