title: Interferon-gamma Inhibits Melanogenesis and Induces Apoptosis in Melanocytes: A Pivotal Role of CD8+ Cytotoxic T Lymphocytes in Vitiligo.
abstract: Increased expression of the cytokine interferon (IFN)-γ plays a pivotal role in vitiligo-induced depigmentation. However, the major source of IFN-γ in vitiligo patients and the mechanisms underlying melanocyte destruction are unknown. In this study, a large number of skin infiltrating IFN-γ+ cells and CD8+ T cells were detected in progressive vitiligo. Among the peripheral blood mononuclear cells (PBMCs) of vitiligo patients, CD8+ cytotoxic T lymphocytes (CTLs) that express IFN-γ exhibited significant expansion, which suggests that activated CTLs are the main source of increased IFN-γ in progressive vitiligo. An in vitro analysis demonstrated that IFN-γ inhibits melanogenesis in primary cultured human melanocytes by altering melanogenic enzyme mRNA expression and, more importantly, that IFN-γ directly induces melanocyte apoptosis. Our data indicate that vitiligo pathophysiology may be linked to globally activated CD8+ CTL subpopulations, which produce increased IFN-γ and induce melanocyte dysfunction and apoptosis.
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Weimin
authors.initials: W
authors.lastname: Shi
authors.forename: Ji
authors.initials: J
authors.lastname: Yang
authors.forename: Lubing
authors.initials: L
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D016827:CD8 Antigens / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000494:pharmacology*; D018655:Lymphocyte Count; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry*; D014820:Vitiligo / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D016827:CD8 Antigens; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D012333:RNA, Messenger; D007371:Interferon-gamma; D014442:Monophenol Monooxygenase