{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:36:04Z","timestamp":1789439764979,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"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":["82473530"],"award-info":[{"award-number":["82473530"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Dysregulated activation of the interleukin\u201021 (IL\u201021)\/IL\u201021 receptor (IL\u201021R) signaling pathway is strongly associated with inflammatory and autoimmune disorders, which positions the pathway as a promising therapeutic target. Given the current lack of approved inhibitors or monoclonal antibodies targeting IL\u201021\/IL\u201021R, we employed a structure\u2010based virtual screening strategy coupled with experimental validation to identify potential IL\u201021 antagonists from a library of marine natural products provided by TargetMol. Our investigation identified fucoxanthin, a marine\u2010derived carotenoid, as a potent binder to IL\u201021R, exhibiting a docking score of \u22128.19\u00a0kcal\/mol. Molecular dynamics simulations further confirmed the stability of the IL\u201021R\u2013fucoxanthin complex, with a calculated binding free energy (\u0394<jats:italic>G<\/jats:italic>) of \u221233.25\u00a0kcal\/mol as determined by MM\/PBSA analysis. Importantly, fucoxanthin demonstrated significant immunomodulatory effects by reducing the frequency of key immune cell populations, including CD19<jats:sup>+<\/jats:sup> B cells, memory B cells, and activated follicular helper CD4<jats:sup>+<\/jats:sup> T (Tfh) cells in cultures of peripheral blood mononuclear cells in vitro. These findings suggest that fucoxanthin acts as a potential IL\u201021 antagonist, offering a novel therapeutic avenue for autoimmune diseases driven by aberrant B\u2010 and T\u2010cell differentiation via the IL\u201021\/IL\u201021R axis.<\/jats:p>","DOI":"10.1002\/cbdv.202402522","type":"journal-article","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T06:29:41Z","timestamp":1739600981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of IL\u201021\/IL\u201021R Signaling by Fucoxanthin: Structure\u2010Based and Experimental Analysis"],"prefix":"10.1002","volume":"22","author":[{"given":"Pinglang","family":"Ruan","sequence":"first","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Provincial People's Hospital  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxiong","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"The First Hospital of Changsha, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8560-0421","authenticated-orcid":false,"given":"Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hunan Key Laboratory of Medical Epigenomics Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.30330"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102019\u2010215089"},{"key":"e_1_2_11_4_1","first-page":"1955","article-title":"Accrual of Organ Damage Over Time in Patients With Systemic Lupus Erythematosus","volume":"30","author":"Gladman D. 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