{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:57:00Z","timestamp":1792180620438,"version":"4.4.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82500624,82341221"],"award-info":[{"award-number":["82500624,82341221"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:p>\n                    Inflammatory bowel disease (IBD) is frequently accompanied by intestinal fibrosis, with nonresponse to long-term anti\u2013TNF-\u03b1 therapy occurring in approximately 23%\u201346% of patients. Integrated analysis of single-cell and bulk RNA-seq datasets revealed an expansion of\n                    <jats:italic>\n                      IL11\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    fibroblasts in inflamed intestine and their significant enrichment in nonresponders. We further identified\n                    <jats:italic>\n                      IL11\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    fibroblasts as a central communication hub that engaged in extensive crosstalk with monocytes and may contribute to inflammatory amplification and fibrotic remodeling. Additionally, we employed machine learning approaches, including least absolute shrinkage and selection operator, support vector machines, and random forest, to derive an\n                    <jats:italic>\n                      IL11\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    fibroblast\u2013related gene signature effectively predicting nonresponse to anti\u2013TNF-\u03b1 in validation and test cohorts. IHC further confirmed the overexpression of IL-11 in nonresponders. The signature genes we found are not only associated with immune and inflammatory responses but also with fibrosis, indicating a robust association between fibrosis and anti\u2013TNF-\u03b1 treatment failure. In summary, this study highlights the important role of\n                    <jats:italic>\n                      IL11\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    fibroblasts in orchestrating both inflammation and fibrosis and provides an applicable model for predicting nonresponse to anti\u2013TNF-\u03b1 in IBD, thereby laying the foundation for precision medicine and targeted therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.198895","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T16:00:56Z","timestamp":1776960056000},"source":"Crossref","is-referenced-by-count":1,"title":["IL11+ fibroblasts are implicated in nonresponse to anti\u2013TNF-\u03b1 via fibrosis in inflammatory bowel 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