{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:39Z","timestamp":1787028579194,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404126"],"award-info":[{"award-number":["82404126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330096"],"award-info":[{"award-number":["82330096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82404126"],"award-info":[{"award-number":["82404126"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82330096"],"award-info":[{"award-number":["82330096"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Xinfei Plan for Boosting Technological Innovation Talent at the Fourth Military Medical University"},{"name":"Xijing Hospital Boosting Program for Innovative Medical Research","award":["XJZT26CX36"],"award-info":[{"award-number":["XJZT26CX36"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitiligo is characterized by epidermal melanocyte destruction, with autoreactive CD8+ T cells playing a central pathogenic role, yet the mechanisms driving their hyperactivation remain unclear. Lactate has emerged as a key immunometabolite that functions as both a signaling molecule and an epigenetic modulator via protein lactylation. Nevertheless, the role of lactate in vitiligo pathogenesis has not been explored. Here, we report that serum lactate levels are significantly elevated in vitiligo patients and correlate positively with disease activity. In a mouse model, lactate administration accelerated vitiligo progression, accompanied by increased CD8+ T cell infiltration and melanocyte destruction in lesional skin. In vitro, lactate enhanced CD8+ T cell effector molecule expression (granzyme B, perforin, IFN-\u03b3, CD107a) and cytotoxic function. Mechanistically, lactate increased global protein lactylation in CD8+ T cells, with marked enrichment at histone H3 lysine 9 (H3K9). H3K9 lactylation (H3K9la) was associated with enhanced chromatin accessibility and transcriptional activation of effector genes, as revealed by RNA sequencing and CUT&amp;Tag analyses. Pharmacological inhibition of lactate production or lactylation abrogated these effects. Collectively, our findings identify lactate as a critical driver of CD8+ T cell pathogenicity in vitiligo through H3K9la-mediated epigenetic reprogramming, highlighting lactate metabolism and lactylation as potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms27093795","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:29:11Z","timestamp":1777033751000},"page":"3795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactate Enhances CD8+ T Cell Cytotoxicity Through H3K9la Upregulation to Drive Vitiligo Pathogenesis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9269-9092","authenticated-orcid":false,"given":"Hang","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luling","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9369-5128","authenticated-orcid":false,"given":"Jianru","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e386","DOI":"10.1016\/S2468-2667(24)00026-4","article-title":"Estimating the burden of vitiligo: A systematic review and modelling study","volume":"9","author":"Akl","year":"2024","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kussainova, A., Kassym, L., Akhmetova, A., Glushkova, N., Sabirov, U., Adilgozhina, S., Tuleutayeva, R., and Semenova, Y. 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