{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:26:51Z","timestamp":1788384411202,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vitiligo is a common autoimmune disorder characterized by melanocyte loss, yet the molecular mechanisms linking genetic susceptibility to melanocyte dysfunction remain incompletely understood. In this study, we integrated multi\u2010tissue transcriptome\u2010wide association studies (TWAS), summary\u2010data\u2010based Mendelian randomization (SMR), and colocalization analyses to identify causal genes within vitiligo susceptibility loci. CTSS was prioritized as a candidate susceptibility gene at the 1q21 locus. Single\u2010cell and bulk RNA sequencing analyses revealed that CTSS was significantly upregulated in lesional melanocytes and associated with an MHC class II\u2010related transcriptional program. Mechanistically, CTSS expression was induced downstream of IFN\u2010\u03b3\/STAT1 signaling and positively associated with oxidative phosphorylation, suggesting potential metabolic regulation. Functional experiments demonstrated that CTSS overexpression was associated with increased HLA\u2010DRA expression, enhanced apoptosis, and reduced proliferation in melanocytes. Furthermore, the selective CTSS inhibitor RO5459072 attenuated HLA\u2010DRA induction in\u00a0vitro. Clinically, serum CTSS levels were elevated in patients with active vitiligo, showed moderate diagnostic performance for disease activity (AUC\u2009=\u20090.787), and correlated with disease severity. Collectively, these findings suggest that CTSS may serve as a key mediator linking genetic susceptibility, inflammatory signaling, and metabolic status in vitiligo. Rather than establishing melanocytes as professional antigen\u2010presenting cells, our results indicate that melanocytes may acquire partial immunogenic features under inflammatory stress conditions. This study provides new insights into melanocyte\u2010intrinsic mechanisms underlying vitiligo pathogenesis and highlights CTSS as a potential therapeutic target for future investigation.<\/jats:p>","DOI":"10.1111\/pcmr.70107","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:29:25Z","timestamp":1782804565000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi\u2010Omics Identifies\n                    <scp>CTSS<\/scp>\n                    as a Susceptibility Gene and Actionable Target That Regulates Melanocyte\n                    <scp>MHC<\/scp>\n                    \u2010\n                    <scp>II<\/scp>\n                    Expression and Survival in Vitiligo"],"prefix":"10.1111","volume":"39","author":[{"given":"Ming\u2010jie","family":"He","sequence":"first","affiliation":[{"name":"Department of Dermatology The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010jia","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Dermatology The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan 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