{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:13:47Z","timestamp":1789172027102,"version":"build-2803163510"},"reference-count":113,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2632026ZD12"],"award-info":[{"award-number":["2632026ZD12"]}],"id":[{"id":"10.13039\/501100012226","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":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Psoriasis (PsO) is a chronic T lymphocyte\u2010mediated inflammatory disease arising on a polygenic background. GL\u2010V9, a structurally optimized flavonoid with reported anti\u2010inflammatory and anti\u2010fibrotic activities, was investigated as a potential therapeutic agent for PsO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The therapeutic and relapse\u2010preventive effects of GL\u2010V9 were evaluated in multiple murine models of psoriasiform inflammation. To define its immunomodulatory actions, we established distinct immune\u2010cell polarization models, including macrophage and T helper cell models, and assessed inflammatory mediator production, immune\u2010cell polarization and intercellular communication within psoriatic lesions. Mechanistic studies further examined the interaction between GL\u2010V9 and tyrosine kinase 2 (TYK2), and the functional relevance of TYK2 using siTYK2\u2010mediated knockdown in bone marrow\u2010derived macrophages and THP\u20101 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>GL\u2010V9 effectively alleviated established psoriasiform dermatitis and reduced disease relapse. Mechanistically, preliminary evidence indicated that GL\u2010V9 binds to the pseudokinase domain of TYK2 and suppresses JAK\/STAT activation, thereby reducing the production of pro\u2010inflammatory cytokines and chemokines. In M1 macrophages and T helper 1 (Th1) cells, GL\u2010V9 disrupted TYK2\u2010dependent signalling, altered pathogenic polarization states and weakened inflammatory communication with neighbouring immune cells, collectively restoring a more balanced immune microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>GL\u2010V9 ameliorates PsO by targeting TYK2\u2013STAT signalling and reshaping macrophage\u2013T helper cell\u2010driven inflammation. These findings support GL\u2010V9 as a promising therapeutic candidate for PsO and other TYK2\u2010mediated inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70603","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:01:55Z","timestamp":1784876515000},"page":"6154-6178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tyrosine kinase 2 inhibition by GL\u2010V9 treats psoriasiform dermatitis via macrophage\u2010helper T\u2010cell modulation"],"prefix":"10.1111","volume":"183","author":[{"given":"Leyi","family":"Chen","sequence":"first","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  Nanjing China"},{"name":"Institute of Chinese Medical Sciences and State Key Laboratory of Mechanism and Quality of Chinese Medicine University of Macau, Avenida da Universidade  Taipa 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