Autoimmune Vitiligo: gene-expression during pathogenesis

描述（由申请人提供）：白癜风是一种常见的获得性色素减退疾病，其特征是表皮黑色素细胞的丢失。虽然白癜风的发病机制尚不清楚，但有证据表明，在许多情况下，白癜风是一种自身免疫性疾病，黑素细胞的丧失是免疫反应的结果。Smyth系（SL）鸡是一种很好的自身免疫性白癜风动物模型，它概括了人类疾病的整个临床和生物学表现。SL白癜风（SLV）的发病和发病率是可预测的，病变容易接近，目标组织再生，从而为研究同一个体SLV发病前和发展过程中病变的演变提供了机会。SL黑素细胞的退化是由异常的黑素细胞活动引起的，这些活动不足以引起没有功能免疫系统的白癜风，但似乎确实涉及引发导致黑素细胞破坏的免疫反应。羽毛中黑色素细胞的丢失与淋巴细胞的浸润和细胞介导的免疫活动有关，包括T辅助细胞、细胞毒性T细胞、IFN- g和凋亡。最后，已知环境因素，即火鸡疱疹病毒（HVT）在这种疾病的发展中起作用。本研究计划的目标是在SLV发展之前和整个过程中研究目标组织（羽毛）中的局部环境。更具体地说，为了确定趋化因子、细胞因子、黑素细胞功能相关蛋白、热休克蛋白和促/抗凋亡蛋白的表达，以及HVT的存在、状态（潜伏或产生）和病毒载量。采用实时定量RT-PCR和免疫印迹的时间过程方法，将用于在SLV发展之前和整个过程中检查这些方面。通过研究靶组织中细胞的活性和反应，在SLV发展之前和整个过程中，将了解白癜风和其他自身免疫性疾病的免疫病理机制。

DESCRIPTION (provided by applicant): Vitiligo is a common acquired hypopigmentary disorder characterized by a loss of epidermal melanocytes. Although the pathogenesis of vitiligo is poorly understood, evidence suggests that in many cases vitiligo is an autoimmune disorder and melanocyte loss is the result of an immunological response. The Smyth line (SL) chicken is an excellent animal model for autoimmune vitiligo that recapitulates the entire spectrum of clinical and biological manifestations of the human disease. The onset and incidence of SL vitiligo (SLV) is predictable, the lesion is easily accessible and the target tissue regenerates, thus providing opportunity to study the evolving lesion prior to and throughout the development of SLV in the same individual. The degeneration of SL melanocytes is preceded by aberrant melanocyte activities that are not sufficient to cause vitiligo without a functioning immune system but do appear to be involved in provoking an immune response resulting in the destruction of melanocytes. Loss of melanocytes in the feather is associated with infiltration of lymphocytes and cell-mediated immune activity, including T helper cells, cytotoxic T cells, IFN- g, and apoptosis. Lastly, an environmental factor, i.e. turkey herpesvirus (HVT), is known to play a role in the development of this disorder. It is the goal of this research proposal to study the local environment in the target tissue (feathers) prior to and throughout the development of SLV. More specifically, to determine the expression of chemokines, cytokines, melanocyte function-associated proteins, heat shock proteins, and pro-/anti-apoptotic proteins, as well as, the presence, state (latent or productive) and viral load of HVT. A time course approach, employing real-time quantitative RT-PCR and immunoblotting, will be used to examine these aspects prior to and throughout the development of SLV. By studying the activities and responses of cells in the target tissue, prior to and throughout the development of SLV, much will be learned about mechanisms involved in the immunopathology of vitiligo and other autoimmune diseases.