{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T21:00:29Z","timestamp":1780174829585,"version":"3.54.0"},"posted":{"date-parts":[[2026,5,27]]},"group-title":"Cell Biology","reference-count":13,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health","award":["R00DK136971"],"award-info":[{"award-number":["R00DK136971"]}]},{"name":"UAB IMPACT funds"},{"name":"UAB Workforce Empowerment Award"},{"name":"UAB Kaul Pediatric Research Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Stem cell-derived organoids are promising platforms for therapeutic screening in inflammatory bowel disease (IBD), but identifying functional organoid readouts with translational utility is challenging. Colon epithelial organoids from patients with ulcerative colitis (UC) overexpress chemokines CXCL1, CXCL11, CCL2, and CCL28, yet whether these inflammatory signatures correlate with disease activity and treatment response is unknown. This short report investigates whether organoid-retained chemokines correlate with disease activity and therapeutic outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We interrogated three bulk and two single-cell transcriptomic datasets from IBD clinical trials encompassing anti-TNF\u03b1 and anti-integrin therapies to determine whether epithelial chemokines retained in UC organoids track clinical response and distinguish treatment responders from non-responders to biologic therapy across multiple IBD patient cohorts.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In bulk transcriptomic data, CXCL1, CXCL11, and CCL2 were elevated in active UC and normalized only in patients achieving clinical remission, independent of therapy class, with persistent chemokine overexpression in non-responders. Single-cell analysis demonstrated widespread chemokine overexpression in UC epithelial clusters, with consistent normalization of CXCL1, CXCL11, and CCL28 in LGR5-positive stem compartment of patients who achieved clinical remission, but not in non-responders. In Crohn\u2019s disease, the resolution of these epithelial chemokines was not associated with clinical response.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Epithelial chemokines, particularly CXCL1, CXCL11, and CCL28, track clinical remission in UC and represent candidate biomarkers and functional endpoints for epithelial-directed therapeutic strategies using stem cell-derived UC organoid models.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.23.727433","type":"posted-content","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:15:24Z","timestamp":1779920124000},"source":"Crossref","is-referenced-by-count":0,"title":["Epithelial stem cell-derived chemokines track clinical remission in inflammatory bowel disease in a disease-specific manner"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9383-229X","authenticated-orcid":false,"given":"Sanmi","family":"Alake","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kadam","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci","family":"Jester","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Maynard","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babajide A.","family":"Ojo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026053013052570000_2026.05.23.727433v1.1","doi-asserted-by":"crossref","first-page":"otae026","DOI":"10.1093\/crocol\/otae026","article-title":"Real-World Patterns and Economic Burden Associated With Treatment Failure With Advanced Therapies in Patients With Moderate-to-Severe Ulcerative Colitis","volume":"6","year":"2024","journal-title":"Crohns Colitis 360"},{"key":"2026053013052570000_2026.05.23.727433v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab161"},{"key":"2026053013052570000_2026.05.23.727433v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20480"},{"key":"2026053013052570000_2026.05.23.727433v1.4","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.07.008"},{"key":"2026053013052570000_2026.05.23.727433v1.5","doi-asserted-by":"publisher","DOI":"10.1093\/ECCO-JCC\/JJAD142"},{"key":"2026053013052570000_2026.05.23.727433v1.6","doi-asserted-by":"crossref","first-page":"11026","DOI":"10.1038\/s41467-025-65988-2","article-title":"Patient-derived colon epithelial organoids reveal lipid-related metabolic dysfunction in pediatric ulcerative colitis","volume":"16","year":"2025","journal-title":"Nat 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