HSP70i is a critical component of the immune response leading to vitiligo.
HSP70i is a critical component of the immune response leading to vitiligo.
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DOI：
10.1111/j.1755-148x.2011.00916.x
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发表时间：
2012-01
影响因子：
4.3
通讯作者：
Poole IC
中科院分区：
文献类型：
--
作者：
Mosenson JA;Zloza A;Klarquist J;Barfuss AJ;Guevara-Patino JA;Poole IC
HSP70 i和其他应激蛋白已被用于抗肿瘤疫苗。这就引出了一个问题，即HSP70 i是否在免疫激活中起着独特的作用。我们用优化的TRP-1（一种高度免疫原性的黑素体靶分子）接种诱导型HSP70 i（Hsp70 - 1）敲除小鼠和野生型动物。我们不能在Hsp70 - 1敲除小鼠中诱导稳健和持久的脱色，并且体内细胞溶解试验显示缺乏CTL活性。没有观察到T细胞浸润到皮肤和毛囊黑素细胞的维持。相比之下，在缺乏组织特异性组成型HSP70同种型（Hsp70 - 2）的小鼠中，用TRP-2接种后，色素脱失无中断地进行。接下来，我们证明了HSP70 i是加速白癜风易感Pmel-1小鼠色素脱失的必要和充分条件，伴随着树突状细胞亚群的持久表型变化。总之，这些研究赋予了HSP70 i在白癜风中的独特功能，并将HSP70 i确定为治疗的靶向实体。
HSP70i and other stress proteins have been used in anti-tumor vaccines. This begs the question whether HSP70i plays a unique role in immune activation. We vaccinated inducible HSP70i (Hsp70-1) knockout mice and wild-type animals with optimized TRP-1, a highly immunogenic melanosomal target molecule. We were unable to induce robust and lasting depigmentation in the Hsp70-1 knockout mice, and in vivo cytolytic assays revealed a lack of CTL activity. Absence of T cell infiltration to the skin and maintenance of hair follicle melanocytes was observed. By contrast, depigmentation proceeded without interruption in mice lacking a tissue specific constitutive isoform of HSP70 (Hsp70-2) vaccinated with TRP-2. Next, we demonstrated that HSP70i was necessary and sufficient to accelerate depigmentation in vitiligo-prone Pmel-1 mice, accompanied by lasting phenotypic changes in dendritic cell subpopulations. In summary, these studies assign a unique function to HSP70i in vitiligo, and identify HSP70i as targetable entity for treatment.