Evidence map›Paper›PMID 24980747›Full record

ArticleThe Journal of experimental medicine2014

Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-γ.

Henner F Farin, Wouter R Karthaus, Pekka Kujala, Maryam Rakhshandehroo, Gerald Schwank, Robert G J Vries, Eric Kalkhoven, Edward E S Nieuwenhuis, Hans Clevers

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed
13.5field-weighted citation impact, top 1% 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

171 citing papers in PubMed, 261 citations in OpenAlex.

  1. Article
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  10. Article
  11. Article
  12. Susceptibility of mice to primaryFrontiers in immunology · 2026
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  13. Article
  14. Gut microbes · 2025
    Article
  15. Article
  16. Invasin-functionalized PIC hydrogels enable long-term 3D culture of epithelial organoids.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. IFN-γ is a direct driver of crypt hyperplasia in celiac disease.The Journal of clinical investigation · 2025
    Article
  18. Mucosal Responses to Type II Interferon in IBD.Inflammatory bowel diseases · 2025
    Article
  19. Article
  20. Review

111 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

9 authors at 3 institutions in 1 country.

Henner F FarinHubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, 3584 CT Utrecht, Netherlands.
Wouter R KarthausHubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, 3584 CT Utrecht, Netherlands.
Pekka KujalaAntoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
Maryam RakhshandehrooSection of Metabolic Diseases, Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.
Gerald SchwankHubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, 3584 CT Utrecht, Netherlands.
Robert G J VriesHubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, 3584 CT Utrecht, Netherlands.
Eric KalkhovenSection of Metabolic Diseases, Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands Netherlands Metabolomics Center, 2333 CC Leiden, Netherlands.
Edward E S NieuwenhuisDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3584 EA Utrecht, Netherlands.
Hans CleversHubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, 3584 CT Utrecht, Netherlands h.clevers@hubrecht.eu.
Hubrecht Institute for Developmental Biology and Stem Cell Research · NLUniversity Medical Center Utrecht · NLThe Netherlands Cancer Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Paneth cells (PCs) are terminally differentiated, highly specialized secretory cells located at the base of the crypts of Lieberkühn in the small intestine. Besides their antimicrobial function, PCs serve as a component of the intestinal stem cell niche. By secreting granules containing bactericidal proteins like defensins/cryptdins and lysozyme, PCs regulate the microbiome of the gut. Here we study the control of PC degranulation in primary epithelial organoids in culture. We show that PC degranulation does not directly occur upon stimulation with microbial antigens or bacteria. In contrast, the pro-inflammatory cytokine Interferon gamma (IFN-γ) induces rapid and complete loss of granules. Using live cell imaging, we show that degranulation is coupled to luminal extrusion and death of PCs. Transfer of supernatants from in vitro stimulated iNKT cells recapitulates degranulation in an IFN-γ-dependent manner. Furthermore, endogenous IFN-γ secretion induced by anti-CD3 antibody injection causes Paneth loss and release of goblet cell mucus. The identification of IFN-γ as a trigger for degranulation and extrusion of PCs establishes a novel effector mechanism by which immune responses may regulate epithelial status and the gut microbiome.

Indexed as

AnimalsAntibodiesCD3 ComplexCell DegranulationDefensinsGoblet CellsInterferon-gammaIntestine, SmallMiceMice, KnockoutMicrobiotaMucusMuramidaseNatural Killer T-CellsOrgan Culture TechniquesPaneth CellsAntibodiesCD3 ComplexDefensinsInterferon-gammaMuramidase

Identifiers

PMID24980747
PMCPMC4076587
OpenAlexW2158068707

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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 OpenQuestion graph.