{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T09:21:24Z","timestamp":1789723284925,"version":"4.0.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008930","name":"CELEST","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008930","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Janus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn\u2019s disease. We aimed to provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from patients with Crohn's disease from CELEST.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Seventy-four patients consented to this optional substudy. Ileal and colonic biopsies were collected during endoscopy at screening and week 12 or 16. RNA isolated from 226 samples was analyzed by RNAseq, with additional qPCR analysis. Additional biopsies from patients with Crohn's disease receiving anti-tumor necrosis factor (anti-TNF; n\u2005=\u200534) and healthy controls (n\u2005=\u200510) were used for qPCR. Single-cell RNAseq public profiles were used to evaluate treatment effects on specific cellular subsets, associations with endoscopic improvement, and indirect comparisons with the anti-TNF-treated cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In involved areas of mucosa with endoscopic remission after upadacitinib treatment, 1156 and 76 protein-coding genes were significantly regulated (false discovery rate &amp;lt; 0.05) at week 12\/16 in colonic and ileal biopsies, respectively (60 overlapped), compared with baseline. Upadacitinib did not significantly affect transcriptomes of noninvolved intestinal areas. CELEST patients (mostly anti-TNF-refractory) showed baseline differences in gene expression compared with a separate cohort of biologic-na\u00efve patients. Notably, upadacitinib reversed overexpression of inflammatory fibroblast and interferon-\u03b3 effector signature markers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Upadacitinib modulates inflammatory pathways in mucosal lesions of patients with anti-TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-\u03b3-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier: NCT02365649)<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izab116","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T11:24:31Z","timestamp":1622114671000},"page":"1999-2009","source":"Crossref","is-referenced-by-count":33,"title":["Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn\u2019s Disease Intestinal Mucosa: Analysis From the CELEST Study"],"prefix":"10.1093","volume":"27","author":[{"given":"Daniel","family":"Aguilar","sequence":"first","affiliation":[{"name":"Hospital Clinic Barcelona, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer , Barcelona , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Instituto de Salud Carlos III , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-2570","authenticated-orcid":false,"given":"Llu\u00eds","family":"Revilla","sequence":"additional","affiliation":[{"name":"Hospital Clinic Barcelona, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer , Barcelona , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Instituto de Salud Carlos III , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Garrido-Trigo","sequence":"additional","affiliation":[{"name":"Hospital Clinic Barcelona, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer , Barcelona , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Instituto de Salud Carlos III , Barcelona , 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