Interferon-gamma Inhibits Melanogenesis and Induces Apoptosis in Melanocytes: A Pivotal Role of CD8+ Cytotoxic T Lymphocytes in Vitiligo
Interferon-gamma Inhibits Melanogenesis and Induces Apoptosis in Melanocytes: A Pivotal Role of CD8+ Cytotoxic T Lymphocytes in Vitiligo
复制标题
干扰素-γ 抑制黑素生成并诱导黑素细胞凋亡：CD8( ) 细胞毒性 T 淋巴细胞在白癜风中的关键作用
DOI：
10.2340/00015555-2080
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发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Li, Ming
中科院分区：
文献类型：
--
作者：
Yang, Lili;Wei, Yi;Li, Ming
细胞因子干扰素-γ的表达增加在白癜风诱导的色素脱失中起着关键作用。然而，白癜风患者干扰素-γ的主要来源和破坏黑素细胞的机制尚不清楚。在本研究中，在进展性白癜风患者的皮肤中检测到大量的干扰素-γ(+)细胞和CD8(+)T细胞。在白癜风患者外周血单个核细胞(PBMC)中，表达干扰素-γ的CD8+细胞毒性T淋巴细胞(CTL)呈明显的增殖状态，提示活化的CTL是进展期白癜风患者升高的主要来源。体外分析表明，干扰素-γ通过改变黑素生成酶基因的表达抑制原代培养的人黑素细胞的黑素生成，更重要的是，干扰素-γ直接诱导黑素细胞的凋亡。我们的数据表明，白癜风的病理生理可能与全球激活的CD8(+)CTL亚群有关，CD8(+)CTL亚群产生增加的干扰素-γ，并诱导黑素细胞功能障碍和细胞凋亡。
Increased expression of the cytokine interferon (IFN)-gamma plays a pivotal role in vitiligo-induced depigmentation. However, the major source of IFN-gamma in vitiligo patients and the mechanisms underlying melanocyte destruction are unknown. In this study, a large number of skin infiltrating IFN-gamma(+) 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-gamma exhibited significant expansion, which suggests that activated CTLs are the main source of increased IFN-gamma in progressive vitiligo. An in vitro analysis demonstrated that IFN-gamma inhibits melanogenesis in primary cultured human melanocytes by altering melanogenic enzyme mRNA expression and, more importantly, that IFN-gamma directly induces melanocyte apoptosis. Our data indicate that vitiligo pathophysiology may be linked to globally activated CD8(+) CTL subpopulations, which produce increased IFN-gamma and induce melanocyte dysfunction and apoptosis.