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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Vitiligo is an autoimmune skin disease mainly mediated by CD8<jats:sup>+<\/jats:sup> T cells, which affects about 0.1%-2% population of the world. <jats:italic>Leptin<\/jats:italic> plays a critical role in regulating the activation of CD8<jats:sup>+<\/jats:sup> T cells. However, the effect of <jats:italic>Leptin<\/jats:italic> on vitiligo remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To explore the effect of leptin on CD8<jats:sup>+<\/jats:sup> T cells and its influence on vitiligo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA sequencing and Quantitative Real-time PCR (RT-qPCR) were used to explore the differentially expressed genes. Immunofluorescence staining was performed on skin lesions. Leptin in serum was detected by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells were detected by flow cytometry after leptin stimulation for 72 hours. A vitiligo model was established by monobenzone on <jats:italic>Leptin<\/jats:italic> KO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>557 differentially expressed genes were found, including 154 up-regulated and 403 down-regulated genes. Lipid metabolism pathways showed a close relationship to the pathogenesis of vitiligo, especially the PPAR signaling pathway. RT-qPCR (p = 0.013) and immunofluorescence staining (p = 0.0053) verified that <jats:italic>LEPR<\/jats:italic> expressed significantly higher in vitiligo. The serum leptin level of vitiligo patients was significantly lower than that of healthy controls (p = 0.0245). The interferon-\u03b3 subset of CD8<jats:sup>+<\/jats:sup>LEPR<jats:sup>+<\/jats:sup> T cells from vitiligo patients was significantly higher (p = 0.0189). The protein level of interferon-\u03b3 was significantly increased after leptin stimulation <jats:italic>in vitro<\/jats:italic> (p = 0.0217). In mice, <jats:italic>Leptin<\/jats:italic> deficiency resulted in less severe hair depigmentation. <jats:italic>Leptin<\/jats:italic> deficiency also resulted in significantly lower expressed vitiligo-related genes, such as <jats:italic>Cxcl9<\/jats:italic> (p = 0.0497)<jats:italic>, Gzmb<\/jats:italic> (p &amp;lt; 0.001)<jats:italic>, Ifng<\/jats:italic> (p = 0.0159), and <jats:italic>Mx1<\/jats:italic> (p &amp;lt; 0.001) after modeling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Leptin<\/jats:italic> could promote the progression of vitiligo by enhancing the cytotoxic function of CD8<jats:sup>+<\/jats:sup> T cells. <jats:italic>Leptin<\/jats:italic> may become a new target for vitiligo treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1158883","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T05:22:55Z","timestamp":1683091375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Leptin deficiency in CD8+ T cells ameliorates non-segmental vitiligo by reducing interferon-\u03b3 and Granzyme B"],"prefix":"10.3389","volume":"14","author":[{"given":"Meiyu","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/S0140-6736(14)60763-7","article-title":"Vitiligo","volume":"386","author":"Ezzedine","year":"2015","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2011.05377.x","article-title":"A review of the worldwide prevalence of vitiligo in children\/adolescents and adults","volume":"51","author":"Kr\u00fcger","year":"2012","journal-title":"Int J Dermatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1111\/j.1755-148X.2012.00997.x","article-title":"Revised classification\/nomenclature of vitiligo and related issues: the vitiligo global issues consensus conference","volume":"25","author":"Ezzedine","year":"2012","journal-title":"Pigment Cell melanoma Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.103067","article-title":"Childhood vitiligo: treatment paradigms","volume":"57","author":"Kanwar","year":"2012","journal-title":"Indian J Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2010.11.061","article-title":"Vitiligo: a comprehensive overview part i. introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up","volume":"65","author":"Alikhan","year":"2011","journal-title":"J Am Acad Dermatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1034\/j.1600-0749.2003.00023.x","article-title":"Evidence for an autoimmune pathogenesis of vitiligo","volume":"16","author":"Ongenae","year":"2003","journal-title":"Pigment Cell Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2010.00773.x","article-title":"Melanin and melanogenesis in adipose tissue: possible mechanisms for abating oxidative stress and inflammation","volume":"12","author":"Page","year":"2011","journal-title":"Obes Rev an Off J Int Assoc Stud Obes"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-1141","article-title":"Insulin resistance is increased in patients with vitiligo","volume":"91","author":"Karadag","year":"2011","journal-title":"Acta dermato-venereol"},{"key":"B9","article-title":"Comparison of serum lipid in girls affected with vitiligo and control group","volume":"55","author":"Pietrzak","year":"2000","journal-title":"Annales Universitatis Mariae Curie-Sklodowska. 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