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The function of TRIM27 in intestinal epithelial cells (IECs), the mechanism by which TRIM27 inhibits the NF\u2010\u03baB pathway and its dysregulation in ulcerative colitis (UC) remain unclear. Here, it is report that epithelial TRIM27 functions as an anti\u2010inflammatory factor that inhibited intestinal inflammation in IECs in vitro and in epithelial\n                    <jats:italic>Trim27<\/jats:italic>\n                    knockout mice in vivo. Mechanistically, TRIM27 destabilized IKK\u03b1 and TRAF6 via polyubiquitination of IKK\u03b1 at the K569 site and TRAF6 at the K489 site. In response to TNF\u2010\u03b1, IKK\u03b2 phosphorylated TRIM27 at S173 to decrease TRIM27 expression by impairing its binding to ubiquitin\u2010specific protease 7 (USP7) and USP7\u2010mediated TRIM27 deubiquitination. Notably, overexpression of TRIM27 enhanced the anti\u2010inflammatory effect of infliximab (IFX) in IECs. TRIM27 is downregulated in inflamed colons from UC patients and is associated with the therapeutic effect of IFX. Overall, this study identifies epithelial TRIM27 as a bona fide negative modulator of intestinal inflammation and USP7\/TRIM27\u2010IKK as a new double negative feedback mechanism of the NF\u2010\u03baB pathway, which supports the use of TRIM27 replenishment as a potential therapeutic strategy for UC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522114","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:07:00Z","timestamp":1776852420000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epithelial TRIM27 Inhibits Intestinal Inflammation in Ulcerative Colitis by the USP7\/TRIM27\u2010IKK Double Negative\u2010Feedback"],"prefix":"10.1002","volume":"13","author":[{"given":"Weimin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, Xinhua Hospital Shanghai Jiaotong University School of Medicine  Shanghai China"},{"name":"Shanghai 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