{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:47:11Z","timestamp":1785775631566,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373877"],"award-info":[{"award-number":["82373877"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430114"],"award-info":[{"award-number":["82430114"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2108085MH320"],"award-info":[{"award-number":["2108085MH320"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease. The kynurenine pathway (KP) of tryptophan metabolism has been implicated in several autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. However, little is known about the role of KP in UC. This study investigated the role of tryptophan 2,3\u2010dioxygenase\u00a0(TDO2), a key rate\u2010limiting enzyme of KP, in UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Dextran sodium sulphate (DSS)\u2010 and 2,4,6\u2010trinitrobenzene sulfonic acid (TNBS)\u2010induced colitis models were used to evaluate the effects of TDO2 deficiency in mice, and the therapeutic potential of pharmacological inhibition was further assessed in the DSS model. In vitro, TDO2 overexpression, small interfering RNA, and the TDO2 inhibitor 680C91 were applied to macrophages and intestinal epithelial cells (IECs) to elucidate underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>TDO2 expression was significantly up\u2010regulated in colonic tissues from UC patients and DSS\u2010induced colitis mice, and was found to colocalise with macrophages and IECs. In macrophages, pharmacological inhibition or knockdown of TDO2 suppressed M1 polarisation and secretory function, whereas kynurenine supplementation restored these effects. In IECs, TDO2 inhibition restored tight junction protein expression and attenuated apoptosis. TDO2 deficiency significantly alleviated disease severity in DSS\u2010 and TNBS\u2010induced colitis models, as reflected by improvements in multiple clinical and histopathological parameters. In the DSS model, TDO2 deficiency or treatment with allopurinol reduced IEC apoptosis and rebalanced macrophage M1\/M2 polarisation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings identify TDO2 as a critical mediator of UC pathogenesis. Targeting TDO2 and KP may provide a promising therapeutic strategy for UC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70521","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:50:48Z","timestamp":1780458648000},"page":"5265-5283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tryptophan 2,3\u2010dioxygenase deficiency attenuates dextran sodium sulphate\u00a0\u2013induced ulcerative colitis in mice by suppressing macrophage polarisation and reducing intestinal epithelial cell apoptosis"],"prefix":"10.1111","volume":"183","author":[{"given":"Weibo","family":"Dong","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology, School of Pharmacy Anhui Medical University  Hefei China"},{"name":"Key Laboratory of Anti\u2010inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education  Hefei 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