Evidence map›Paper›PMID 39937025›Full record

ArticleCells2025

Neutralizing IL-15 Inhibits Tissue-Damaging Immune Response in Ex Vivo Cultured Untreated Celiac Intestinal Mucosa.

Vera Rotondi Aufiero, Giuseppe Iacomino, Giovanni De Chiara, Errico Picariello, Gaetano Iaquinto, Riccardo Troncone, Giuseppe Mazzarella

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Interleukin 15 and autoimmune disorders: pathophysiology, therapeutic potential, and clinical implications.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  4. Review
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

7 authors.

Vera Rotondi AufieroInstitute of Food Science, National Research Council (ISA-CNR), 83100 Avellino, Italy.
Giuseppe IacominoInstitute of Food Science, National Research Council (ISA-CNR), 83100 Avellino, Italy.ORCID 0000-0001-5231-2231
Giovanni De ChiaraAnatomic Pathology Unit, San G. Moscati Hospital, 83100 Avellino, Italy.ORCID 0000-0003-0894-8544
Errico PicarielloInstitute of Food Science, National Research Council (ISA-CNR), 83100 Avellino, Italy.
Gaetano IaquintoGastroenterology Unit, S. Rita Hospital, 83100 Avellino, Italy.
Riccardo TronconeEuropean Laboratory for the Investigation of Food Induced Diseases (ELFID), Via Pansini 5, 80131 Napoli, Italy.ORCID 0000-0002-1345-5819
Giuseppe MazzarellaInstitute of Food Science, National Research Council (ISA-CNR), 83100 Avellino, Italy.ORCID 0000-0002-7294-8277

Funding

Fondazione Celiachia FC 2017_014. 2017_014.
6 · The paper itself

Abstract

In celiac disease (CeD), interleukin 15 (IL-15) affects the epithelial barrier by acting on intraepithelial lymphocytes, promoting interferon γ (IFN-γ) production and inducing strong cytotoxic activity as well as eliciting apoptotic death of enterocytes by the Fas/Fas ligand system. This study investigates the effects of a monoclonal antibody neutralizing the effects of IL-15 (aIL-15) on tissue-damaging immune response in untreated CeD patients by using an organ culture system. Jejunal biopsies from 10 untreated CeD patients were cultured ex vivo with or without aIL-15. Epithelial expressions of CD95/Fas, HLA-E and perforin were analyzed by immunohistochemistry. Apoptosis was detected in the epithelium by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Additionally, the surface epithelium compartment of ex vivo cultured biopsy samples was isolated by laser capture microdissection (LCM). RNA from each LCM sample was extracted and the relative expression of IFN-γ was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). Biopsies cultured with the aIL-15 antibody showed a reduction in Fas, HLA-E and perforin epithelial expression, as well as a decrease in epithelial TUNEL+ cells compared to biopsies cultured without the aIL-15 antibody. Moreover, downregulation of epithelial IFN-γ expression was recorded in biopsies incubated with aIL-15, compared to those cultured without aIL-15. Our findings suggest that neutralizing the effects of IL-15 in ex vivo cultured untreated CeD intestinal mucosa could block apoptosis by downregulating Fas and HLA-E expression and the release of cytotoxic proteins, such as perforin. Furthermore, it can dampen the hyperactive immune response by reducing IFN-γ expression. More generally, our study provides new evidence for the effects of anti-IL-15 neutralizing monoclonal antibodies in preventing or repairing epithelial damage and further supports the concept that IL-15 is a meaningful therapeutic target in CeD, or inflammatory diseases associated with the upregulation of IL-15.

Indexed as

Antibodies, NeutralizingCeliac DiseaseImmunityInterleukin-15Intestinal MucosaAdultApoptosisfas ReceptorFemaleHLA-E AntigensHumansInterferon-gammaMaleMiddle AgedPerforinAntibodies, Neutralizingfas ReceptorHLA-E AntigensIL15 protein, humanInterferon-gammaInterleukin-15Perforinceliac diseasecytotoxicityIL-15therapy

Identifiers

PMID39937025
PMCPMC11818035

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Registered trials

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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.