{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:48:50Z","timestamp":1790804930503,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fibrosis and inflammation frequently emerge soon after ileal resection for strictures in Crohn\u2019s disease (CD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study examined the profibrotic and proinflammatory effects of conditioned media from TNF and IFN-\u03b3 (T+I)-exposed healthy and inactive CD ileal enteroids (CDiE) on subepithelial myofibroblasts (SEMF), modeling early post-ileal resection conditions in CD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ileal enteroids from healthy subjects (HE) and inactive CD patients (CDiE) were exposed to T+I for 6 hours, followed by an 18-hour conditioning period. Conditioned media were collected and applied to human intestinal myofibroblasts (HIMF) from healthy and inactive CD ileum for 24 hours to assess proinflammatory and profibrotic gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      T+I exposure induced epithelial damage and cell death in CDiE, while reducing proliferation and decreasing occludin and F-actin expression in both HE and CDiE. TEER (transepithelial electrical resistance) declined in CDiE but remained stable in HE. Conditioned media from T+I-exposed enteroids altered HIMF-HC (healthy control) and HIMF-CD mRNA expression, upregulating proinflammatory genes (\n                      <jats:italic>IL1B<\/jats:italic>\n                      ,\n                      <jats:italic>IL6<\/jats:italic>\n                      ,\n                      <jats:italic>MCP1<\/jats:italic>\n                      , and\n                      <jats:italic>IKBA<\/jats:italic>\n                      ) while downregulating profibrotic genes (\n                      <jats:italic>COL1A1<\/jats:italic>\n                      ,\n                      <jats:italic>ACTA2<\/jats:italic>\n                      ,\n                      <jats:italic>TGFB<\/jats:italic>\n                      , and\n                      <jats:italic>SRF<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Cytokine-exposed HE- and CDiE-derived conditioned media promoted inflammation while suppressing fibrosis-associated gene expression in subepithelial myofibroblasts. Our results suggest that damaged intestinal crypts in early CD inflammation may not directly trigger certain fibrogenic markers\n                      <jats:italic>in vitro<\/jats:italic>\n                      . This model of the early post-ileal resection state provides a platform to identify key targets for preventing fibrosis progression and potentially reducing the need for repeat ileal surgery in CD patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1764088","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:05:00Z","timestamp":1776258300000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A model for Crohn\u2019s disease post-ileal resection fibrosis development using human ileal enteroids and myofibroblasts"],"prefix":"10.3389","volume":"17","author":[{"given":"Jun Hwan","family":"Yoo","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine","place":["Baltimore, MD, United States"]},{"name":"Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine","place":["Seongnam, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Jeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine","place":["Seongnam, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna V.","family":"Pinchuk","sequence":"additional","affiliation":[{"name":"Department of Medicine, Penn State Health Milton S. 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