{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:55:25Z","timestamp":1792551325434,"version":"4.5.0"},"reference-count":78,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KU Leuven Internal Funds","award":["C12\/15\/016"],"award-info":[{"award-number":["C12\/15\/016"]}]},{"name":"KU Leuven Internal Funds","award":["C14\/17\/097"],"award-info":[{"award-number":["C14\/17\/097"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,15]]},"abstract":"<jats:p>Crohn\u2019s disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.<\/jats:p>","DOI":"10.1172\/jci173835","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T12:04:09Z","timestamp":1721736249000},"source":"Crossref","is-referenced-by-count":54,"title":["Intercellular interaction between FAP+ fibroblasts and CD150+ inflammatory monocytes mediates fibrostenosis in Crohn\u2019s disease"],"prefix":"10.1172","volume":"134","author":[{"given":"Bo-Jun","family":"Ke","sequence":"first","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Abdurahiman","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-8865","authenticated-orcid":true,"given":"Francesca","family":"Biscu","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."},{"name":"Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Zanella","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Dragoni","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."},{"name":"Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Santhosh","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"De Simone","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anissa","family":"Zouzaf","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lies","family":"van Baarle","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Stakenborg","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Bos\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic."},{"name":"International Clinical Research Center, St. Anne\u2019s University Hospital Brno, Brno, Czech Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2443-5864","authenticated-orcid":true,"given":"Yentl","family":"Van Rymenant","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Verhulst","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sare","family":"Verstockt","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Immunology and Respiratory Research, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Bislenghi","sequence":"additional","affiliation":[{"name":"Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Wolthuis","sequence":"additional","affiliation":[{"name":"Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Fri\u010d","sequence":"additional","affiliation":[{"name":"International Clinical Research Center, St. Anne\u2019s University Hospital Brno, Brno, Czech Republic."},{"name":"International Clinical Research Center, Faculty of Medicine, Masaryk University, Brno, Czech Republic."},{"name":"Institute of Hematology and Blood Transfusion, Prague, Czech Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-1068","authenticated-orcid":true,"given":"Christine","family":"Breynaert","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"D\u2019Hoore","sequence":"additional","affiliation":[{"name":"Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Van der Veken","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"De Meester","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lovisa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-9325","authenticated-orcid":true,"given":"Lukas J.A.C.","family":"Hawinkels","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3898-7093","authenticated-orcid":true,"given":"Bram","family":"Verstockt","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."},{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"De Hertogh","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, University Hospitals Leuven, Leuven, Belgium."},{"name":"Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9942-3019","authenticated-orcid":true,"given":"S\u00e9verine","family":"Vermeire","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."},{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Matteoli","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium."},{"name":"Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32448-0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.150"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21371"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.224154"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.043372"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.07.041"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2017.393"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199905063401804"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.208"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.09.078"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318440"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056818"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-021-01041-7"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa166"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.008"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.002"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.029"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01520-5"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.08.033"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjw126"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1021\/jm500031w"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2435-4"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.92"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0196-y"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1070"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32552-1"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1028"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1663-x"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0292-x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.07.007"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-17-0298"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247652"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199612000-00011"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620059114"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03256-0"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13465"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.57"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208470"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05274-6"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.12.005"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.08.016"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1263-7"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29366-6"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320318110"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1972"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0594"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1546-z"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00071.2019"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30602"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.02.015"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.9.4659"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1602OC"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051839"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-68993-1"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.07.014"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2018.11.005"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.73600.1"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02547-0"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa1009"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"B66","unstructured":"CellTypist. Automated cell type annotation for scRNA-seq datasets. https:\/\/www.celltypist.org\/ Accessed June 20, 2024."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03852-1"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0336-2"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"B73","unstructured":"Nishimura D. BioCarta. https:\/\/www.liebertpub.com\/doi\/abs\/10.1089\/152791601750294344?journalCode=bsi Accessed June 20, 2024"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz849"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.018"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01044-w"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01018-x"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3791\/53691"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/173835\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:13:57Z","timestamp":1779232437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/173835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,23]]},"references-count":78,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8,15]]},"published-print":{"date-parts":[[2024,8,15]]}},"alternative-id":["10.1172\/JCI173835"],"URL":"https:\/\/doi.org\/10.1172\/jci173835","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.05.04.539383","asserted-by":"object"}]},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,23]]},"article-number":"e173835"}}