{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:28:59Z","timestamp":1790886539616,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vitiligo is an acquired skin depigmentation disorder resulting from the selective loss of epidermal melanocytes, and previous studies have suggested that a T lymphocyte\u2010mediated mechanism has a role in melanocyte loss. Although Fas\u2010Fas ligand (FasL) interactions are important for T lymphocytes to mediate cytotoxicity, there are only few reports examining the involvement of the Fas\u2010FasL pathway in vitiligo using in vivo mouse models. In addition, there have been no reports concerning Fas\u2010mediated apoptosis in human melanocytes in vitro. In this study, we found that the Fas\u2010mediated pathway is involved in cytotoxic T lymphocyte (CTL)\u2010dependent vitiligo in a mouse model and FasL\u2010induced apoptosis of human melanocytes. Tumor necrosis factor (TNF)\u2010\u03b1 and interferon (IFN)\u2010\u03b3, the expression levels of which have been reported to be elevated in lesional skin of patients with vitiligo, synergistically upregulated Fas expression on human melanocytes but inhibited the Fas\u2010mediated apoptosis. Treatment with TNF\u2010\u03b1 and IFN\u2010\u03b3 synergistically upregulated the expression of the anti\u2010apoptotic genes, <jats:italic>c\u2010IAP2<\/jats:italic>, <jats:italic>c\u2010FLIP<\/jats:italic> and <jats:italic>MCL1<\/jats:italic>. A siRNA knock\u2010down study showed that <jats:italic>c\u2010FLIP<\/jats:italic> and <jats:italic>MCL1<\/jats:italic>, but not <jats:italic>c\u2010IAP2<\/jats:italic>, were involved in inducing synergistic inhibitory effects on Fas\u2010mediated apoptosis. Furthermore, we found that FasL and TNF\u2010related apoptosis<jats:bold>\u2010<\/jats:bold>inducing ligand (TRAIL) synergistically induced apoptosis on human melanocytes. In conclusion, our results suggest that the Fas\u2010FasL pathway is involved in CTL\u2010dependent vitiligo and the elevated expression levels of TNF\u2010\u03b1 and IFN\u2010\u03b3 in lesional skin may act synergistically on melanocytes to suppress Fas\u2010mediated apoptosis.<\/jats:p>","DOI":"10.1111\/exd.14053","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T18:35:33Z","timestamp":1572633333000},"page":"61-70","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Fas\u2010FasL interaction in cytotoxic T cell\u2010mediated vitiligo: The role of lesional expression of tumor necrosis factor\u2010\u03b1 and interferon\u2010\u03b3 in Fas\u2010mediated melanocyte apoptosis"],"prefix":"10.1111","volume":"29","author":[{"given":"Haruki","family":"Jimbo","sequence":"first","affiliation":[{"name":"Division of Dermatology Department of Internal Related Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3779-9085","authenticated-orcid":false,"given":"Hiroshi","family":"Nagai","sequence":"additional","affiliation":[{"name":"Division of Dermatology Department of Internal Related Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Division of Dermatology Department of Internal Related Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Shimoura","sequence":"additional","affiliation":[{"name":"Division of Dermatology Department of Internal Related Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikako","family":"Nishigori","sequence":"additional","affiliation":[{"name":"Division of Dermatology Department of Internal Related Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2011.05377.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-017-8622-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.6.1203"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.32"},{"key":"e_1_2_8_6_1","first-page":"1219","volume":"148","author":"Le Poole I. 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