{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:57:48Z","timestamp":1793228268990,"version":"4.5.0"},"reference-count":54,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81873555"],"award-info":[{"award-number":["81873555"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"crossref","award":["SHDC2025CCS019"],"award-info":[{"award-number":["SHDC2025CCS019"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:p>Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, characterized by ongoing intestinal inflammation, epithelial damage, and mucosal injury. Despite the identification of C-C motif chemokine ligand 5 (CCL5) as a key mediator in UC, the precise mechanisms underlying its role in immune activation and inflammation remain unclear. This study aimed to investigate CCL5 as a critical immune modulator in UC, focusing on its effects on immune cell activation, particularly regulatory T cell (Treg) formation, and the molecular pathways involved in these processes. Using the dextran sulfate sodium salt (DSS)-induced UC model and CCL5 knockout (Ccl5-KO) mice, we demonstrated that CCL5 deficiency exacerbates intestinal inflammation during the acute phase of colitis, partly due to impaired interleukin-33 (IL-33)-induced Treg formation. In addition, we observed a positive correlation between CCL5 expression and forkhead box protein 3 (FOXP3) levels in inflamed colon tissues of UC patients, suggesting a role for CCL5 in Treg regulation. Mechanistically, CCL5 deficiency disrupted the PI3K\/Akt\/NF-\u03baB signaling pathway, resulting in reduced IL-33 expression, which in turn impaired CD4+ T cell activation and FOXP3+ Treg formation via the JAK1\/STAT5 pathway. In vivo rescue experiments confirmed that restoring IL-33 signaling could alleviate inflammation and partially recover Treg function. Collectively, these findings highlight CCL5 as a novel immune modulator of Treg formation and immune responses in UC and suggest that targeting CCL5 may offer a promising therapeutic strategy for managing UC and related inflammatory diseases.<\/jats:p>","DOI":"10.1042\/cs20256734","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T17:06:28Z","timestamp":1766509588000},"page":"27-46","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CCL5 deficiency aggravates acute DSS-induced colitis by restricting IL-33-induced formation of Tregs in intestinal tract"],"prefix":"10.1042","volume":"140","author":[{"given":"Yang","family":"Luo","sequence":"first","affiliation":[{"name":"1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Yue","family":"Gong","sequence":"additional","affiliation":[{"name":"1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Heng","family":"Zhao","sequence":"additional","affiliation":[{"name":"1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Yao","family":"Ye","sequence":"additional","affiliation":[{"name":"1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"2State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R., China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8478-3342","authenticated-orcid":false,"given":"Ming","family":"Zhong","sequence":"additional","affiliation":[{"name":"3Department of General Surgery, Gongli Hospital, 219 Miaopu Road, Pudong New District, Shanghai, P.R., 200135, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"2026011406063224000_CS-2025-6734C1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"2026011406063224000_CS-2025-6734C2","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1126\/science.7569902","article-title":"Activation of dual T cell signaling pathways by the chemokine RANTES","volume":"269","author":"Bacon","year":"1995","journal-title":"Science"},{"key":"2026011406063224000_CS-2025-6734C3","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1172\/JCI118861","article-title":"Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses","volume":"98","author":"Berg","year":"1996","journal-title":"J. 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