Creating an experimental animal model of alopecia areata

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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.