{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:50:15Z","timestamp":1791589815035,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871276"],"award-info":[{"award-number":["81871276"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon\u2010\u03b3\u2010inducible protein 16 (IFI16) was reported to be involved in the pathogenesis of Beh\u00e7et's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real\u2010time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (<jats:italic>P<\/jats:italic>\u2009=\u20090.012). The plasma TNF\u2010\u03b1 protein level in intestinal BS was significantly higher than in healthy controls (HCs; <jats:italic>P<\/jats:italic>\u2009=\u20090.009). PBMCs of intestinal BS patients and HCs were co\u2010cultured with human normal IECs (NCM460) to explore the interaction between immunological cells and IECs. Using <jats:italic>IFI16<\/jats:italic> knockdown, PBMC\u2010NCM460 co\u2010culture, TNF\u2010\u03b1 neutralizing monoclonal antibody (mAb), stimulator of interferon genes (STING) agonist 2\u20323\u2032\u2010cGAMP, and the PLK1 inhibitor SBE 13 HCL, we found that PLK1 promotes the secretion of TNF\u2010\u03b1 from PBMCs of intestinal BS patients, which causes overexpression of <jats:italic>IFI16<\/jats:italic> and induces apoptosis of IECs via the STING\u2013TBK1 pathway. The expressions of IFI16, TNF\u2010\u03b1, cleaved caspase 3, phosphorylated STING (pSTING) and phosphorylated tank binding kinase 1 (pTBK1) in the intestinal ulcer tissue of BS patients were significantly higher than that of HCs (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). PLK1 in PBMCs of intestinal BS patients increased TNF\u2010\u03b1 secretion, inducing IEC apoptosis via activation of the IFI16\u2013STING\u2013TBK1 pathway. PLK1 and the IFI16\u2013STING\u2013TBK1 pathway may be new therapeutic targets for intestinal BS.<\/jats:p>","DOI":"10.1111\/febs.17147","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T18:35:10Z","timestamp":1714242910000},"page":"3432-3453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>PLK<\/scp>1\u2010activating <scp>IFI<\/scp>16\u2013<scp>STING<\/scp>\u2013<scp>TBK<\/scp>1 pathway induces apoptosis of intestinal epithelial cells in patients with intestinal Beh\u00e7et's syndrome"],"prefix":"10.1111","volume":"291","author":[{"given":"Hua\u2010fang","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Huadong Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010hui","family":"She","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and 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