{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T18:18:59Z","timestamp":1788286739249,"version":"build-2803163510"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-133607"],"award-info":[{"award-number":["MOP-133607"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Crohn 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\u2032-phosphatase-deficient (SHIP\u2212\/\u2212) mouse develops spontaneous Crohn disease\u2013like ileal inflammation and fibrosis. Fibrosis depends on increased phosphatidylinositol 3-kinase p110\u03b4 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We 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-1\u03b2 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\u2212\/\u2212 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Blocking or genetic ablation of IL-13, but not IL-4, significantly reduced ileal fibrosis in mice, including collagen accumulation, smooth muscle thickening, vimentin\u2009+\u2009cells, and proliferating vimentin\u2009+\u2009cells. Blockade of IL-13 also reduced intestinal inflammation, including immune cell infiltration and ileal IL-1\u03b2 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\u2212\/\u2212 mice similarly showed increased ileal mast cells that were also a source of IL13.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IL-13 is critical for intestinal fibrosis in SHIP-deficient mice, and mast cells are a source of IL13 in Crohn disease\u2013associated intestinal fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izag127","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T18:35:25Z","timestamp":1783535725000},"page":"1783-1799","source":"Crossref","is-referenced-by-count":0,"title":["Mast cell\u2013derived IL-13 as a driver of Crohn disease\u2013associated intestinal fibrosis"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3959-485X","authenticated-orcid":false,"given":"Kwestan","family":"Safari","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children\u2019s Hospital Research Institute , Vancouver, British Columbia, V5Z 4H4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Jen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children\u2019s Hospital Research Institute , Vancouver, British Columbia, V5Z 4H4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhreet","family":"Sekhon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children\u2019s Hospital Research Institute , Vancouver, British Columbia, V5Z 4H4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children\u2019s Hospital Research Institute , Vancouver, British Columbia, V5Z 4H4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan C","family":"Menzies","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children\u2019s Hospital Research Institute , Vancouver, British Columbia, V5Z 4H4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine , Kurume, Fukuoka, 830-0011,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Fratzscher","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, the University of British Columbia and British Columbia Cancer Research Centre , Vancouver, British Columbia, V5Z 1L3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3422-8823","authenticated-orcid":false,"given":"Andrew","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, the University of British Columbia and British Columbia Cancer Research Centre , Vancouver, British Columbia, V5Z 1L3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Medicine, and Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta , Edmonton, Alberta, T6G 2H5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M","family":"Sly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, the University of British Columbia and BC Children\u2019s Hospital Research Institute , Vancouver, British Columbia, V5Z 4H4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"2026090114023206700_izag127-B1","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41586-020-2025-2","article-title":"Pathway paradigms revealed from the genetics of inflammatory bowel disease","volume":"578","author":"Graham","year":"2020","journal-title":"Nature"},{"key":"2026090114023206700_izag127-B2","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1177\/2050640620901960","article-title":"Natural history, diagnosis and treatment 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