Creating an experimental animal model of alopecia areata

描述(申请人提供)：斑秃是一种慢性自身免疫性疾病 影响0.2-2%人口的脱发障碍。虽然斑秃 是一种非致命性疾病，疾病本身和治疗并发症都可以 导致严重的发病率。研究的临床和实验室数据 人类患者提示斑秃可能由自身反应性引起 淋巴细胞，尤其是CD8+T淋巴细胞。虽然被动转移 实验描绘了一旦自身反应性T细胞脱发的过程 淋巴细胞的形成是一种循序渐进的免疫事件 疾病的发生、发展和维持的原因 目前仍不清楚。此外，自身反应性淋巴细胞靶向的抗原 仍然不为人知。此外，目前还没有活跃的实验动物 斑秃模型解剖这些循序渐进的事件。少年派， 劳伦斯·S·陈，医学博士，曾受过免疫皮肤科研究员的训练。 凯文·D·库珀是这所大学的细胞免疫学家。来自密歇根州。对于 目前的提议是，PI旨在表征一种新产生的小鼠模型 由小鼠毛发皮下免疫引起的脱发障碍 卵泡基底膜成分。这个新生成的活动鼠标模型 脱发障碍的临床和组织学结果与人类相似 斑秃。一些受影响的小鼠产生了对该病毒的自身抗体 免疫原。同一品系的小鼠产生了自身反应性T细胞反应 自身蛋白质。PI建议将此模型验证为鼠标模型 治疗人类脱发。面积，具体目标如下：1)。身份验证 这种脱发紊乱模型的自身免疫性。表征 效应器免疫细胞类型。如果被确立为人类疾病的模型， 这可能有助于阐明人类斑秃的发病机制。 从而导致最终针对人类的靶向特异性免疫治疗 病人。

DESCRIPTION (provided by applicant): Alopecia areata is a chronic autoimmune hair loss disorder that affects 0.2-2 % of population. Although alopecia areata is a non-fatal disease, the disease itself and the treatment complication can cause significant morbidity. Clinical and laboratory data from studying of human patients suggests that alopecia areata may be caused by autoreactive lymphocytes, particularly CD8+ T lymphocytes. Although passive transfer experiments delineated the hair loss process once the autoreactive T lymphocytes are formed, the step-by-step immunological sequence of events accounting for the initiation, progression, and maintenance of the disease remain unclear. Moreover, the antigen targeted by the autoreactive lymphocytes remains unknown. Furthermore, currently there is no active experimental animal model of alopecia areata for dissecting these step by-step events. The PI, Lawrence S. Chan, M.D., was trained as a fellow in Immuno-dermatology under Dr. Kevin D. Cooper, a cellular immunologist at the Univ. of Michigan. For the current proposal, the PI aims at characterizing a newly generated mouse model of hair loss disorder, induced by subcutaneous immunization of a mouse hair follicle basement membrane component. This newly generated active mouse model of hair loss disorder has clinical and histologic findings resembling the human disease alopecia areata. Some affected mice developed autoantibodies to the immunogens. The same strain of mice developed autoreactive T cell response to the self proteins. The PI proposes to authenticate this model as a mouse model for human alopecia. areata with the following specific aims: 1). Authentication of the autoimmune nature of this hair loss disorder model 2). Characterization of the effector immune cell types. If established as a model of human disease, it may shed light to the pathogenesis of alopecia areata in human patients and thereby lead to eventual target-specific immunological treatments for human patients.