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While emerging evidence indicates an association between the type I interferons (I\u2010IFNs) signature and the initiation of the immune response, it remains unclear whether I\u2010IFNs function as a critical mediator in the vitiligo initiation phase. Their precise molecular mechanisms of action necessitate further investigation. I\u2010IFNs mainly include subtypes IFN\u03b1, IFN\u03b2, and IFN\u03ba. In our study, we observed markedly elevated levels of IFN\u03b2 in both peripheral blood and perilesional skin of vitiligo patients. Then, employing multiple vitiligo models and IFNAR\u2010deficient mice, we proved that IFN\u03b2 signaling through the IFNAR1\/IFNAR2 receptor is critically required for disease initiation. Mechanically, IFN\u03b2 directly induced melanocyte apoptosis. In addition, it specifically induced melanocytes, but not keratinocytes, to secrete the chemokines CXCL9\/10\/11. These chemokines subsequently recruited cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells to the epidermis, amplifying the immune response and ultimately leading to melanocyte destruction. Finally, intervention with triptolide\u2014a potent IFN\u03b2 inhibitor derived from the medicinal plant\n                    <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                    \u2014confirmed that suppressing IFN\u03b2 signaling can inhibit the initiation of vitiligo.\n                  <\/jats:p>","DOI":"10.1096\/fj.202504606r","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T12:16:56Z","timestamp":1771071416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Type I Interferons Induce\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T Cell Chemotaxis Through Regulating Melanocyte but Not Keratinocyte\n                    <scp>CXCL9<\/scp>\n                    \/10\/11 Secretion in the Initiation of Vitiligo"],"prefix":"10.1096","volume":"40","author":[{"given":"Da","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"Development and Planning Department Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixian","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6767-5529","authenticated-orcid":false,"given":"Huali","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.797026"},{"issue":"12","key":"e_1_2_12_3_1","article-title":"The Pathogenesis and Management of Vitiligo","volume":"16","author":"Albelowi L. 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