Evidence map›Paper›PMID 42418669›Full record

ArticleInflammatory bowel diseases2026

Mast cell-derived IL-13 as a driver of Crohn disease-associated intestinal fibrosis.

Kwestan Safari, Wei Jen Ma, Prabhreet Sekhon, Priya Rai, Susan C Menzies, Tomoaki Hoshino, Anne-Sophie Fratzscher, Andrew Roth, Karen Madsen, Laura M Sly

Abstract read
In one paragraph

Article in Inflammatory bowel diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Kwestan SafariDepartment of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, V5Z 4H4, Canada.ORCID 0000-0002-3959-485X
Wei Jen MaDepartment of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, V5Z 4H4, Canada.
Prabhreet SekhonDepartment of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, V5Z 4H4, Canada.
Priya RaiDepartment of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, V5Z 4H4, Canada.
Susan C MenziesDepartment of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, V5Z 4H4, Canada.
Tomoaki HoshinoDepartment of Internal Medicine, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan.
Anne-Sophie FratzscherDepartment of Molecular Oncology, the University of British Columbia and British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada.
Andrew RothDepartment of Molecular Oncology, the University of British Columbia and British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada.ORCID 0000-0003-3422-8823
Karen MadsenDepartment of Medicine, and Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Alberta, T6G 2H5, Canada.
Laura M SlyDepartment of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, V5Z 4H4, Canada.

Funding

CIHR MOP-133607
6 · The paper itself

Abstract

backgroundCrohn disease is a chronic, immune-mediated disease that can lead to intestinal fibrosis, strictures, and bowel obstruction. The Src homology 2 domain-containing inositol polyphosphate 5'-phosphatase-deficient (SHIP-/-) mouse develops spontaneous Crohn disease-like ileal inflammation and fibrosis. Fibrosis depends on increased phosphatidylinositol 3-kinase p110δ activity downstream of interleukin 4 (IL-4) or IL-13. Because current anti-inflammatory treatments do not prevent or reverse fibrosis, we aimed to identify the key cytokine(s) and its cellular source(s).

methodsWe blocked IL-4 or IL-13 in mice by use of neutralizing antibodies or genetic ablation. Intestinal inflammation and fibrosis were assessed by gross pathology, histopathology, collagen accumulation, muscle thickening, immune cell infiltration, and tissue IL-1β concentrations. IL13 and its cellular source in stricturing Crohn disease were examined using single-cell RNA sequencing and RNAscope. Mast cells and Il13 were also assessed in ileal cross-sections from SHIP+/+ and SHIP-/- mice.

resultsBlocking or genetic ablation of IL-13, but not IL-4, significantly reduced ileal fibrosis in mice, including collagen accumulation, smooth muscle thickening, vimentin + cells, and proliferating vimentin + cells. Blockade of IL-13 also reduced intestinal inflammation, including immune cell infiltration and ileal IL-1β concentrations. Single-cell RNA-sequencing analyses identified mast cells as the exclusive source of IL13 in stricturing Crohn disease. Human resection tissues confirmed increased mast cells in diseased small intestine and identified mast cells as the source of IL13. SHIP-/- mice similarly showed increased ileal mast cells that were also a source of IL13.

conclusionsIL-13 is critical for intestinal fibrosis in SHIP-deficient mice, and mast cells are a source of IL13 in Crohn disease-associated intestinal fibrosis.

Indexed as

Crohn DiseaseFibrosisInterleukin-13Mast CellsAnimalsDisease Models, AnimalHumansInterleukin-4MaleMiceMice, Inbred C57BLMice, KnockoutPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesInterleukin-13Interleukin-4Phosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesCrohn disease fibrosisinterleukin-13mast cellsSH2 domain-containing inositol polyphosphate 5'-phosphatase

Identifiers

PMID42418669
PMCPMC13533194

What Socratic holds

Textmetadata
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.