{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T18:03:31Z","timestamp":1785261811380,"version":"3.55.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Irish Research Council under the Pathway program","award":["21\/PATH-S\/9621"],"award-info":[{"award-number":["21\/PATH-S\/9621"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Interactions between fibroblasts and monocytes have emerged as a contributing factor in inflammatory bowel disease (IBD) pathogenesis and therapy resistance, owing to the ability of both cell types to participate in tissue inflammation and repair. We have previously shown that the tumor necrosis factor superfamily member TWEAK (TNFSF12) can induce an ulcerative colitis (UC)-like inflammatory profile in colonic fibroblasts in vitro, in turn promoting monocyte adhesion and activation. However, the mechanisms underlying fibroblast\u2013monocyte communication and its dysregulation in ulcerative colitis are incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we use co-culture models, human biopsies from UC patients and healthy donors, and public single-cell transcriptomics to characterize the mechanisms underlying fibroblast-mediated monocyte activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that TWEAK-treated inflammatory fibroblasts induce a transcriptional program that resembles early monocyte\/macrophage intermediates in UC and is enriched for genes associated with resistance to anti-TNF (TREM1, OSM, IL1B) and susceptibility to IBD (NOD2, ATG16L1). We find that conditioned media from TWEAK-treated fibroblasts causes a sustained activation of STAT3 phosphorylation in monocytes, and that inhibition of the NF-\u03baB inducing kinase (NIK) impairs the ability of inflammatory fibroblasts to activate STAT3 phosphorylation in monocytes, resulting in reduced expression of inflammatory mediators. Using tissues from UC patients, we show that the expansion of CD90+\/PDPN+ inflammatory fibroblasts and increased FN14 in UC correlates with the accumulation of TWEAK+ myeloid cells in the colonic mucosa, and that these fibroblasts co-localize with infiltrating monocytes in sites of active inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, our findings suggest that the TWEAK\/NF-\u03baB\/STAT3 axis represents an attractive target to tune inflammatory stroma\/monocyte crosstalk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag012","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T12:39:25Z","timestamp":1769863165000},"source":"Crossref","is-referenced-by-count":1,"title":["TWEAK is increased in ulcerative colitis and contributes to fibroblast-mediated monocyte activation via heterologous non-canonical NF-kB\/STAT3 signaling"],"prefix":"10.1093","volume":"20","author":[{"given":"Carlos","family":"Matellan","sequence":"first","affiliation":[{"name":"School of Biomolecular and Biomedical Sciences, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"School of Medicine, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Raphael","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Sciences, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth R","family":"Jones","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, University of Glasgow , Glasgow,","place":["Scotland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Nwaeziegwe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St. Vincent\u2019s University Hospital , Elm Park, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Balfe","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Sciences, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cian M","family":"Ohlendieck","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Sciences, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bauset","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Sciences, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9abh B","family":"N\u00ed Chathail","sequence":"additional","affiliation":[{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"School of Public Health, Physiotherapy, and Sports Science, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciar\u00e1n","family":"Kennedy","sequence":"additional","affiliation":[{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"School of Medicine, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"Diabetes Complications Research Centre, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Doogan","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Sciences, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Des","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St. Vincent\u2019s University Hospital , Elm Park, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol M","family":"Aherne","sequence":"additional","affiliation":[{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"School of Medicine, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M","family":"Roche","sequence":"additional","affiliation":[{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"School of Public Health, Physiotherapy, and Sports Science, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"Institute for Global Food Security, Queen\u2019s University Belfast , Belfast,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calum C","family":"Bain","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, University of Glasgow , Glasgow,","place":["Scotland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D","family":"Thorpe","sequence":"additional","affiliation":[{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"School of Medicine, University College Dublin , Belfield, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen","family":"Doherty","sequence":"additional","affiliation":[{"name":"UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin,","place":["Ireland"]},{"name":"Department of Gastroenterology, St. Vincent\u2019s University Hospital , Elm Park, Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario 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