{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:16:14Z","timestamp":1790878574203,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Society of Vitiligo","award":["20K08660"],"award-info":[{"award-number":["20K08660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitiligo is a chronic autoimmune dermatosis defined by selective melanocyte depletion and patchy depigmentation. IFN\u2013\u03b3-driven recruitment of autoreactive CD8+ T cells and induction of melanocyte apoptosis are central to its pathogenesis. Current therapies\u2014including UVB phototherapy, tacrolimus, vitamin D3 analogs, and surgical methods\u2014show limited and inconsistent efficacy. Emerging treatments like JAK inhibitors and WNT activators offer potential but require further validation. Translational progress is hindered by a lack of scalable human models. Here, we describe a tunable in vitro vitiligo platform in which human iPSC-derived melanocytes (iMc) are co-cultured with keratinocytes on Matrigel and exposed to precise graded IFN-\u03b3 concentrations. Our data revealed dose-dependent decreases in iMc survival and dendritic structure, faithfully mirroring derived melanocyte pathology. Leveraging this platform, we first evaluated the short-term efficacy of the ROCK inhibitor Y27632 under early-stage patient IFN-\u03b3 concentrations representative of patient lesional thresholds. At three days, Y27632 significantly upregulated adhesion molecules E-cadherin and DDR1, and two central factors\u2014ET1 and bFGF. Importantly, ROCK inhibition reversed dendritic retraction and improved overall viability of iMc-keratinocytes. These findings position ROCK blockade as a promising adjunctive strategy and establish a pre-clinical platform for evaluating combination therapies for durable pigment restoration.<\/jats:p>","DOI":"10.3390\/ijms26168069","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:40:48Z","timestamp":1755765648000},"page":"8069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Linking IFN-\u03b3-Mediated Pathogenesis to ROCK-Targeted Therapy in a Scalable iPSCs-Based Vitiligo Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Toshiro","family":"Komatsu","sequence":"first","affiliation":[{"name":"Division of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8037-1455","authenticated-orcid":false,"given":"Yupeng","family":"Dong","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaharu","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamihiro","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Miyagi, Japan"},{"name":"Kawakami Dermatology Clinic, Matsudo 270-0034, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","first-page":"160","article-title":"Clinical Practice. 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