A similar local immune and oxidative stress phenotype in vitiligo and halo nevus
A similar local immune and oxidative stress phenotype in vitiligo and halo nevus
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白癜风和晕痣具有相似的局部免疫和氧化应激表型
DOI：
10.1016/j.jdermsci.2017.03.008
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发表时间：
2017-07-01
影响因子：
4.6
通讯作者：
Jian, Zhe
中科院分区：
文献类型：
--
作者：
Yang, Yuqi;Li, Shuli;Jian, Zhe
背景：白癜风和晕痣是两种常见的T细胞介导的皮肤病。虽然自身免疫已被认为是参与这两种疾病，白癜风和晕痣之间的关系是不完全understood.Objective：目前的研究的目的是调查是否白癜风和晕痣共享相同的免疫和氧化应激反应。T细胞浸润和趋化因子受体表达采用免疫组织化学方法检测白癜风和晕痣病变中的CXCR 3、CCR 4、CCR 5和细胞毒性标志物（颗粒酶B、PerforM）。采用酶联免疫吸附试验（ELISA）检测正常人、白癜风患者和晕痣患者外周血单个核细胞中趋化因子和CD 8（+）T细胞分泌的细胞毒标志物的表达。通过qRT-PCR分析确定健康对照、白癜风患者和晕痣患者中趋化因子受体和CXCR 3配体的组织水平。流式细胞术检测外周血CXCR 3（+）CD 4（+）T细胞和CXCR 3（+）CD 8（+）T细胞的百分比。结果：免疫组化结果显示白癜风和晕痣皮损中有明显的T细胞反应，真皮中CD 8（+）T细胞浸润明显。炎症细胞毒性标记物如颗粒酶B和穿孔蛋白在白癜风和晕痣中也升高，表明原位炎症反应。通过qRT-PCR和ELISA检测，我们发现趋化因子受体CXCR 3及其配体在白癜风和晕痣皮损中的表达显著增加，尤其是CXCL 10的积累。此外，H2 O2的水平，参与调节免疫反应的关键球员是显着上调白癜风和晕痣的皮肤病变。此外，白癜风和晕痣皮损中H2 O2浓度升高与CXCL 10水平呈正相关。这些结果表明白癜风和晕痣中存在H2 O2参与的自身免疫表型，其特征在于IFN-γ诱导的趋化因子对CXCL 10-CXCR 3水平增加，以及皮肤病变中密集的CD 8（+）T浸润，这表明这两种疾病的发病机制相似。(C)2017由Elsevier爱尔兰有限公司代表日本皮肤病研究学会发布。
Background: Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood.Objective: The aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response.Methods: Infiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, PerforM) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry. Enzyme-linked immunosorbent assay was performed to analyze the expressions of chemokines in the serum samples and cytotoxic markers secreted by CD8(+) T cells which were sorted from the peripheral blood mononuclear cells in healthy donors, vitiligo and halo nevus patients. Tissue levels of chemokine receptors and CXCR3 ligands in healthy controls, vitiligo patients and halo nevus patients were determined by qRT-PCR analysis. The percentages of CXCR3(+) CD4(+) T and CXCR3(+) CD8(+) T cells from the peripheral blood samples were examined by flow cytometry. Tissue and serum hydrogen peroxide (H2O2) concentrations were measured using H2O2 assay kit.Results: Immunohistochemistry revealed a significant T-cell response, with pronounced dermal infiltrates of CD8(+) T cells in vitiligo and halo nevus. The inflammatory cytotoxic markers such as Granzyme B and Perforin were also elevated in vitiligo and halo nevus, suggesting inflammatory responses in situ. By qRT-PCR and ELISA assay, we found significantly increased expressions of the chemokine receptor CXCR3 and its ligands, especially the accumulated CXCL10 in the skin lesions of vitiligo and halo nevus. Moreover, the level of H2O2, a key player involved in regulation of the immune response was significantly upregulated in the skin lesions of vitiligo and halo nevus. In addition, the increased H2O2 concentration correlated positively with CXCL10 level in skin lesions of vitiligo and halo nevus.Conclusions: These results demonstrate a H2O2-involved autoimmune phenotype in vitiligo and halo nevus, characterized by increased level of IFN-gamma-inducible chemokine pair CXCL10-CXCR3, as well as a dense CD8(+) T infiltration in the skin lesions, thus suggesting a similar pathogenesis of the two diseases. (C) 2017 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.