title: Dysregulation of melanocyte function by Th17-related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris.
abstract: The aim of this study was to determine whether CD4(+) IL-17A(+) Th17 cells infiltrate vitiligo skin and to investigate whether the proinflammatory cytokines related to Th17 cell influence melanocyte enzymatic activity and cell fate. An immunohistochemical analysis showed Th17 cell infiltration in 21 of 23 vitiligo skin samples in addition to CD8(+)  cells on the reticular dermis. An in vitro analysis showed that the expression of MITF and downstream genes was downregulated in melanocytes by treatment with interleukin (IL)-17A, IL-1β, IL-6, and tumor necrosis factor (TNF)-α. Treatment with these cytokines also induced morphological shrinking in melanocytes, resulting in decreased melanin production. In terms of local cytokine network in the skin, IL-17A dramatically induced IL-1β, IL-6, and TNF-α production in skin-resident cells such as keratinocytes and fibroblasts. Our results provide evidence of the influence of a complex Th17 cell-related cytokine environment in local depigmentation in addition to CD8(+)  cell-mediated melanocyte destruction in autoimmune vitiligo.
authors.affiliation: Department of Dermatology Integrated Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Kotobuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanemura
authors.forename: Lingli
authors.initials: L
authors.lastname: Yang
authors.forename: Saori
authors.initials: S
authors.lastname: Itoi
authors.forename: Mari
authors.initials: M
authors.lastname: Wataya-Kaneda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D014820:Vitiligo / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D012333:RNA, Messenger; D018121:Receptors, Cytokine