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: Lili Yang, Yi Wei, Yue Sun, Weimin Shi, Ji Yang, Lubing Zhu, Ming Li
• Journal: Acta dermato-venereologica (Acta Derm Venereol) Vol. 95 Issue 6 Pg. 664-70 (Jul 2015) ISSN: 1651-2057 [Electronic] Sweden
• PMID: 25721262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD8 Antigens
• MITF protein, human
• Melanins
• Microphthalmia-Associated Transcription Factor
• RNA, Messenger
• Interferon-gamma
• Monophenol Monooxygenase

Topics

• Adult
• Apoptosis (drug effects)
• CD8 Antigens (analysis)
• Cells, Cultured
• Female
• Gene Expression (genetics)
• Humans
• Interferon-gamma (analysis, pharmacology)
• Lymphocyte Count
• Male
• Melanins (biosynthesis)
• Melanocytes (drug effects, enzymology, physiology)
• Microphthalmia-Associated Transcription Factor (genetics)
• Middle Aged
• Monophenol Monooxygenase (genetics)
• Primary Cell Culture
• RNA, Messenger (metabolism)
• Skin (chemistry, cytology)
• T-Lymphocytes, Cytotoxic (chemistry)
• Vitiligo (immunology, pathology)
• Young Adult