{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:35:44Z","timestamp":1779334544576,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82303984"],"award-info":[{"award-number":["82303984"]}]},{"name":"National Natural Science Foundation of China","award":["82273513"],"award-info":[{"award-number":["82273513"]}]},{"name":"National Natural Science Foundation of China","award":["2022CFB746"],"award-info":[{"award-number":["2022CFB746"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["82303984"],"award-info":[{"award-number":["82303984"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["82273513"],"award-info":[{"award-number":["82273513"]}]},{"name":"Natural Science Foundation of Hubei Province","award":["2022CFB746"],"award-info":[{"award-number":["2022CFB746"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autoimmune CD8+ T cell-driven melanocyte destruction constitutes a key pathogenic mechanism in the development of vitiligo. Therefore, the pharmacological inhibition of CD8+ T cell effector functions and skin trafficking is a clinically viable therapeutic strategy. This study investigates leflunomide (LEF), an immunomodulatory drug with established safety in autoimmune diseases, for its therapeutic potential in a tyrosine-related protein (TRP) 2-180-induced vitiligo mouse model. Through flow cytometry, immunofluorescence, ELISA, and histopathological analyses, we systematically evaluated LEF\u2019s effects on T cell regulation, chemokine expression, and cytokine profiles. Key findings demonstrated that LEF (20 mg\/kg\/day) significantly attenuated depigmentation by reducing CD8+ T cell infiltration and suppressing the IFN-\u03b3-driven expression of CXCL9\/10. Furthermore, LEF restored CD4+\/CD8+ T cell homeostasis and rebalanced pro-inflammatory (IFN-\u03b3, TNF-\u03b1, IL-2) and anti-inflammatory (IL-4, IL-10) cytokines, inducing a shift from Th1 to Th2. These results position LEF as an effective immunomodulator that disrupts the IFN-\u03b3-CXCL9\/10 axis and re-establishes immune balance, offering a promising repurposing strategy for halting vitiligo progression.<\/jats:p>","DOI":"10.3390\/ijms26146787","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T15:01:05Z","timestamp":1752591665000},"page":"6787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Leflunomide-Mediated Immunomodulation Inhibits Lesion Progression in a Vitiligo Mouse Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Fang","family":"Miao","sequence":"first","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengmeng","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuhuan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-6967","authenticated-orcid":false,"given":"Ying","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiechi","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/pcmr.12974","article-title":"Vitiligo: Translational Research and Effective Therapeutic Strategies","volume":"34","author":"Thakur","year":"2021","journal-title":"Pigment. 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