Recent advances in understanding vitiligo.
Recent advances in understanding vitiligo.
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DOI：
10.12688/f1000research.8976.1
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Orlow, Seth J
中科院分区：
文献类型：
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作者：
Manga, Prashiela;Elbuluk, Nada;Orlow, Seth J
白癜风是一种获得性色素脱失疾病，表现为皮肤上的白色斑，可引起明显的心理压力和污名化。最近的进展揭示了驱动疾病发作和进展以及治疗方法的关键组成部分。白癜风可以通过对皮肤黑色素产生细胞黑色素细胞的压力而引发。这些触发因素，从晒伤到机械创伤和化学暴露，最终导致针对黑素细胞的自身免疫反应，推动进行性皮肤色素脱失。我们对疾病病因学的理解在三个方面取得了最重要的进展：（1）识别细胞对应激的反应，包括抗氧化途径和未折叠蛋白反应（UPR），作为疾病发作的关键参与者，（2）表征靶向黑素细胞并驱动疾病进展的免疫反应，以及（3）识别主要易感基因。目前白癜风发病机制的模型假设氧化应激导致细胞破坏，包括内质网（ER）中蛋白质成熟的中断，导致UPR的激活和UPR调节的趋化因子（如白细胞介素6（IL-6）和IL-8）的表达。这些趋化因子将免疫成分募集到皮肤，导致黑素细胞被靶向破坏。氧化应激可通过促进抗原呈递进一步增加黑素细胞靶向。促进疾病进展的自身免疫应答的两个关键组分是干扰素（IFN）-γ/CXCL 10轴和IL-17介导的应答。一些全基因组关联研究支持这些途径的作用，抗氧化基因NRF 2，UPR基因XBP 1和许多免疫相关基因，包括I类和II类主要组织相容性基因，与白癜风的发生风险相关。促进白癜风色素沉着的新方法正在研究中，可能会产生有效，持久的治疗。
Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-gamma/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.