{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:48:33Z","timestamp":1791607713219,"version":"4.3.4"},"reference-count":101,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016834","name":"Chongqing Municipal Health Commission","doi-asserted-by":"publisher","award":["2025MSXM078"],"award-info":[{"award-number":["2025MSXM078"]}],"id":[{"id":"10.13039\/100016834","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302060"],"award-info":[{"award-number":["82302060"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders of the gastrointestinal tract driven by immune dysregulation. In recent years, increasing attention has been directed toward the role of the thymus in the pathogenesis of IBD. However, a comprehensive and systematic review on this topic remains lacking. This article focuses on the immunoregulatory function of the thymus in IBD, emphasizing its pivotal role in maintaining intestinal immune homeostasis through the development and function of regulatory T cells (Tregs). We systematically review the mechanisms by which the thymic microenvironment, transcription factors, signaling pathways, and intercellular interactions regulate Treg homeostasis. Additionally, we propose the concept of the \u201cgut\u2010thymus axis,\u201d elucidating how intestinal microbiota dysbiosis can impair thymic structure and function\u2014primarily via TLR signaling pathways\u2014thereby reducing Treg output, establishing a pro\u2010inflammatory positive feedback loop, and exacerbating IBD progression. We further note that although thymus\u2010targeted therapeutic strategies have been extensively explored\u2014including thymectomy, ex\u00a0vivo expansion and in\u00a0vivo induction of Tregs, molecular targeting of signaling pathways, and thymic microenvironment remodeling\u2014the translational maturity of these strategies varies considerably. In summary, thymic dysfunction may contribute to the pathogenesis of IBD by disrupting Treg\u2010mediated central immune tolerance; nevertheless, its core pathogenic role in human IBD requires further clinical validation. Future research leveraging emerging technologies such as single\u2010cell omics and organoid models may further elucidate gut\u2010thymus crosstalk mechanisms and offer theoretical foundations and therapeutic targets for precision immunotherapy in IBD.<\/jats:p>","DOI":"10.1002\/cph4.70188","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T03:45:51Z","timestamp":1780285551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the Gut: How the Thymus Reshapes the Immune Landscape of Inflammatory Bowel Disease"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1929-1829","authenticated-orcid":false,"given":"Yannan","family":"Ma","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Affiliated Hospital Army Medical University  Chongqing China"},{"name":"Department of Gastroenterology, The Second Affiliated 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