Cellular stress and innate inflammation in organ-specific autoimmunity: lessons learned from vitiligo.
Cellular stress and innate inflammation in organ-specific autoimmunity: lessons learned from vitiligo.
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DOI：
10.1111/imr.12369
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发表时间：
2016-01
影响因子：
8.7
通讯作者：
Harris JE
中科院分区：
文献类型：
--
作者：
Harris JE
几十年来，自身免疫的研究主要集中在免疫对疾病的贡献上。然而，最近的研究报道，在自身免疫靶向的细胞中，活性氧（ROS）水平升高和未折叠蛋白反应（UPR）的异常激活，暗示来自靶组织的细胞应激是一个促成因素。更好地理解这一贡献可能有助于回答器官特异性自身免疫中重要的遗留问题，比如什么因素引发疾病，什么因素指导其组织特异性。白癜风是一种皮肤自身免疫性疾病，30多年来一直是转化研究的重点，黑素细胞应激和免疫机制一直被认为是相互排斥的发病机制。化学诱导的白癜风是一种独特的临床表现，反映了环境影响对自身免疫的重要性，提供了一种将细胞应激与免疫反应联系起来的新范式，并可作为其他自身免疫性疾病的模板。在这篇综述中，我将讨论细胞应激对许多自身免疫性疾病的影响的证据，仍然存在的问题，以及白癜风，一个被低估的器官特异性自身免疫的例子，如何帮助回答这些问题。
For decades, research in autoimmunity has focused primarily on immune contributions to disease. Yet recent studies report elevated levels of reactive oxygen species (ROS) and abnormal activation of the unfolded protein response (UPR) in cells targeted by autoimmunity, implicating cellular stress originating from the target tissue as a contributing factor. A better understanding of this contribution may help to answer important lingering questions in organ-specific autoimmunity, like what factors initiate disease, and what directs its tissue specificity. Vitiligo, an autoimmune disease of the skin, has been the focus of translational research for over 30 years, and both melanocyte stress and immune mechanisms have been thought to be mutually exclusive explanations for pathogenesis. Chemical-induced vitiligo is a unique clinical presentation that reflects the importance of environmental influences on autoimmunity, provides insight into a new paradigm linking cell stress to the immune response, and serves as a template for other autoimmune diseases. In this review I will discuss the evidence for cell stress contributions to a number of autoimmune diseases, the questions that remain, and how vitiligo, an underappreciated example of organ-specific autoimmunity, helps to answer them.