Creating an experimental animal model of alopecia areata

描述（由申请人提供）：斑秃是一种慢性自身免疫性疾病， 影响0.2- 2%人口的脱发病症。虽然斑秃 是一种非致命性疾病，疾病本身和治疗并发症可以 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是由自身反应性的 淋巴细胞，特别是CD 8 + T淋巴细胞。虽然被动转移 实验描绘了脱发的过程，一旦自身反应T 淋巴细胞形成，一步一步的免疫学事件序列 解释疾病的发生、发展和维持 仍然不清楚。此外，自身反应性淋巴细胞靶向的抗原 仍然未知。此外，目前还没有活跃的实验动物， 斑秃的模型来解剖这些一步一步的事件。私家侦探， Lawrence S. Chan，医学博士，在Dr. 凯文·D密歇根大学的细胞免疫学家库珀说。为 目前的提议，PI旨在表征新生成的小鼠模型 脱发的障碍，诱导皮下免疫小鼠的头发 卵泡基底膜成分这个新生成的活跃小鼠模型 脱发疾病的临床和组织学发现类似于人类 疾病斑秃。一些受影响的小鼠产生了针对 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建议将此模型认证为小鼠模型 治疗人类脱发具体目标如下：（1）。认证 这种脱发疾病模型的自身免疫性质2）。表征 效应免疫细胞类型。如果建立人类疾病模型， 它可能揭示人类患者斑秃的发病机制， 从而导致最终的靶特异性免疫治疗 患者

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.