Evidence map›Paper›PMID 28550196›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2017

IL-6 Signaling Regulates Small Intestinal Crypt Homeostasis.

Victoria Jeffery, Andrew J Goldson, Jack R Dainty, Marcello Chieppa, Anastasia Sobolewski

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
3.9field-weighted citation impact, top 5% of its field
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

66 citing papers in PubMed, 103 citations in OpenAlex.

  1. Trial
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  5. Article
  6. Treg-specific IL-6R signaling: a novel role in the regulation of the intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Frontiers in immunology · 2024
    Article
  17. Review
  18. Liver organoid culture methods.Cell & bioscience · 2023
    Review
  19. Recent Advances in Cell-Based In Vitro Models to Recreate Human Intestinal Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  20. Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Victoria JefferySchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
Andrew J GoldsonGut Health and Food Safety Institute Strategic Program, Quadram Institute Bioscience, Norwich NR4 7UA, United Kingdom.ORCID 0000-0002-7132-2459
Jack R DaintyNorwich Medical School, University of East Anglia, Norwich NR4 7UQ, United Kingdom; and.
Marcello ChieppaNational Institute of Gastroenterology "Saverio de Bellis," Institute of Research, Castellana Grotte 70013, Italy.ORCID 0000-0001-9819-0823
Anastasia SobolewskiSchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom; a.sobolewski@uea.ac.uk.
University of East Anglia · GBGastroenterology Hospital "Saverio de Bellis" · ITQuadram Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J004529/1Biotechnology and Biological Sciences Research Council BB/J014524/1Wellcome Trust
6 · The paper itself

Abstract

Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells. Immunolabeling studies showed that the IL-6 receptor was restricted to the basal membrane of Paneth cells both in vitro and in vivo and that the crypt epithelium also expressed IL-6. Either a blocking Ab to the IL-6 receptor or a neutralizing Ab to IL-6 significantly reduced in vitro basal crypt organoid proliferation and budding, and in vivo significantly reduced the number of nuclei and the number of Lgr5EGFP-positive stem cells per crypt compared with IgG-treated mice, with the number of Paneth cells per crypt also significantly reduced. Functional studies demonstrated that IL-6-induced in vitro crypt organoid proliferation and crypt budding was abrogated by the Wnt inhibitor IWP2. This work demonstrates that autocrine IL-6 signaling in the gut epithelium regulates crypt homeostasis through the Paneth cells and the Wnt signaling pathway.

Indexed as

HomeostasisWnt Signaling PathwayAnimalsCell DifferentiationCell ProliferationGene Expression RegulationImmunoglobulin GInterleukin-6Intestinal MucosaIntestine, SmallMiceOrgan Culture TechniquesPaneth CellsReceptors, Interleukin-6STAT3 Transcription FactorStem CellsImmunoglobulin GInterleukin-6Receptors, Interleukin-6Stat3 protein, mouseSTAT3 Transcription Factor

Identifiers

PMID28550196
PMCPMC6485663
OpenAlexW2618460085

What OpenQuestion holds

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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 OpenQuestion graph.