HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo
HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo
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DOI：
10.1038/jid.2008.45
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发表时间：
2008-08-01
影响因子：
6.5
通讯作者：
Le Poole, I. Caroline
中科院分区：
文献类型：
--
作者：
Denman, Cecele J.;McCracken, James;Le Poole, I. Caroline
白癜风是一种T细胞介导的皮肤自身免疫性疾病。渐进的脱位会响应压力加速。个人创伤，与漂白酚的接触，过度暴露于紫外线以及机械损伤会导致黑素细胞的逐渐丧失。这项研究的重点是应激蛋白热休克蛋白（HSP）70在将应激转化为自身免疫性疾病为黑素细胞的作用。细胞内HSP70可以充当细胞保护剂，可防止胁迫下细胞的凋亡。同工型HSP70I可以由活细胞分泌，在先前的体外研究中，HSP70已显示可激活树突状细胞并引起对伴侣蛋白和肽的免疫反应。在这里，HSP70在沉淀和永久性白癜风中的作用在体内在自身免疫性白癜风的小鼠模型中进行了评估。在该模型中，通过基因枪疫苗接种，具有编码黑色素细胞分化抗原的真核表达质粒来引入脱位。在该模型中，在疫苗接种方案中纳入人类和小鼠诱导的HSP70在疫苗接种方案中显着增加和加速了降级，并伴随着延长对HSP70的体液响应。对靶标的细胞毒性与A（B）限制的酪氨酸酶相关蛋白2衍生的肽与脱位相关的靶标。提供的数据强烈支持在体内进行性逐渐降低的HSP70I的作用。
Vitiligo is a T-cell-mediated autoimmune disease of the skin. Progressive depigmentation accelerates in response to stress. Personal trauma, contact with bleaching phenols, overexposure to UV, and mechanical injury can lead to progressive loss of melanocytes. This study was focused on the role of stress protein heat shock protein (HSP)70 for translating stress into an autoimmune disease to melanocytes. Intracellular HSP70 can act as a cytoprotectant, preventing apoptosis in cells under stress. Isoform HSP70i can be secreted by live cells, and in prior in vitro studies, HSP70 has been shown to activate dendritic cells and elicit an immune response to chaperoned proteins and peptides. Here, the role of HSP70 in precipitating and perpetuating vitiligo was assessed in vivo in a mouse model of autoimmune vitiligo. In this model, depigmentation was introduced by gene gun vaccination with eukaryotic expression plasmids encoding melanocyte differentiation antigens. Inclusion of human and mouse-derived inducible HSP70 in the vaccination protocol significantly increased and accelerated depigmentation in this model, accompanied by the induction of prolonged humoral responses to HSP70. Cytotoxicity toward targets loaded with a K(b)-restricted tyrosinase-related protein 2-derived peptide correlated with depigmentation. The data presented strongly support a role for HSP70i in progressive depigmentation in vivo.