Understanding mechanisms of autoimmunity through translational research in vitiligo.
Understanding mechanisms of autoimmunity through translational research in vitiligo.
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DOI：
10.1016/j.coi.2016.09.008
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发表时间：
2016-12
影响因子：
7
通讯作者：
Harris JE
中科院分区：
文献类型：
--
作者：
Strassner JP;Harris JE
白癜风是一种皮肤自身免疫性疾病，会导致改变生活的色素脱失，并且仍然难以治疗。然而，超过30-40年的临床观察和转化性研究已经导致了疾病发病机制的一个有洞察力的工作模型的发展：跨越免疫和黑素细胞功能的遗传风险被已知和可疑的环境因素推到超过阈值，从而启动自身免疫T细胞介导的黑素细胞杀伤。在细胞应激下，黑素细胞似乎发出先天免疫信号来激活T细胞。一旦自身免疫T细胞应答建立，IFN-γ-STAT1-CXCL10信号轴成为驱动白癜风进展和维持的主要炎症途径。对于现有的和正在开发的药物来说，这一途径是一个诱人的目标，但进一步详细说明黑素细胞如何发出自己死亡的信号，也可能导致新的治疗靶点。白癜风的研究可能是未来了解器官特异性自身免疫发病机制的关键，因为白癜风是常见的，可逆的，在个体的一生中进展，已经相对明确，并且很容易使用转化和临床方法进行研究。在这些研究中揭示的东西可以导致创新的治疗方法，也有助于阐明类似器官特异性自身免疫性疾病的原理，特别是在目标器官不易接近的情况下。
Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible.