A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte.

A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte.
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DOI:
10.1186/s13619-022-00132-9
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发表时间:
2022-10-02
期刊:
影响因子:
--
通讯作者:
Chen, Ting
Chen, Ting
中科院分区:
其他
文献类型:
--
作者:
Chen, Daoming;Xu, Zijian;Cui, Jun;Chen, Ting

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白癜风是人类最常见的皮肤色素脱失性疾病。它由破坏皮肤黑素细胞的内源性自身反应性CD 8 + T细胞介导。据估计,这种疾病的患病率为全球人口的1%,目前尚无治愈方法。动物模型是理解白癜风发病机制和开发新疗法不可或缺的工具。在这里,我们描述了一种白癜风小鼠模型,它概括了白癜风的关键临床特征,包括表皮色素脱失,皮肤中的CD 8 + T细胞浸润和黑素细胞丢失。为了激活靶向黑素细胞的内源性自身反应性细胞毒性CD 8 + T细胞,该模型依赖于B16 F10黑色素瘤细胞的瞬时接种和CD 4+调节性T细胞的耗竭。在细胞水平,表皮CD 8 + T细胞浸润和黑素细胞损失早在治疗后第19天开始。2个月后出现肉眼可见的表皮色素脱失。该方案可仅使用市售试剂在任何C57 BL/6背景小鼠品系中有效诱导白癜风。这使研究人员能够利用小鼠遗传学工具进行深入的体内白癜风研究,并为药物发现提供了强大的平台。
Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies. Here, we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo, including epidermis depigmentation, CD8 + T cell infiltration in skin, and melanocyte loss. To activate endogenous autoreactive cytotoxic CD8 + T cells targeting melanocytes, this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4 + regulatory T cells. At cellular level, epidermal CD8 + T cell infiltration and melanocyte loss start as early as Day 19 after treatment. Visually apparent epidermis depigmentation occurs 2 months later. This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain, using only commercially available reagents. This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools, and provides a powerful platform for drug discovery.
DOI: 10.1038/ng.3680
发表时间: 2016-11
期刊: NATURE GENETICS
影响因子: 30.8
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发表时间: 2014-11
影响因子: 4.3
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DOI: 10.1056/nejmoa061592
发表时间: 2007-03-22
影响因子: 158.5
作者:
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通讯作者: Spritz, Richard A.
DOI: 10.1186/s12955-020-1278-7
发表时间: 2020-02-03
影响因子: 3.6
作者:
Hamidizadeh, Nasrin;Ranjbar, Sara;Handjani, Farhad
通讯作者: Handjani, Farhad
DOI: 10.1001/jamadermatol.2015.2707
发表时间: 2016-01-01
期刊: JAMA DERMATOLOGY
影响因子: 10.9
作者:
Hua, Camille;Boussemart, Lise;Robert, Caroline
通讯作者: Robert, Caroline