Understanding autoimmunity of vitiligo and alopecia areata.
Understanding autoimmunity of vitiligo and alopecia areata.
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DOI：
10.1097/mop.0000000000000375
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发表时间：
2016-08
影响因子：
3.6
通讯作者：
Harris JE
中科院分区：
文献类型：
--
作者：
Rork JF;Rashighi M;Harris JE
白癜风和斑秃是常见的，毁容皮肤病。治疗选择是有限的，包括非靶向方法，如皮质类固醇，局部钙调磷酸酶抑制剂，窄带UVB光疗，和其他免疫调节剂。本文的目的是回顾白癜风和斑秃之间共享的新机制，并讨论它们如何为未来靶向治疗的发展提供信息。白癜风和斑秃都是自身免疫性疾病，并且在先天性和适应性免疫系统水平上已经确定了发病机制的惊人相似性。增加的活性氧和高细胞应激水平已被认为是这两种疾病中先天免疫系统的起始触发因素，并且全基因组关联研究涉及影响先天免疫和适应性免疫的风险等位基因。最重要的是，在白癜风和斑秃小鼠模型中的机制研究特别涉及IFN-γ驱动的免疫应答，包括IFN-γ、IFN-γ诱导的趋化因子和细胞毒性CD 8 + T细胞作为疾病发病机制的主要驱动因素。这些最近的发现可能揭示了开发新治疗方法的有效策略，一些概念验证临床研究支持这一假设。IFN-γ驱动的免疫信号通路的鉴定使得能够发现白癜风和斑秃的潜在新治疗方法，并支持启动更大规模的临床试验。
Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials.