066 Gene expression profiling of alopecia areata in human disease and the C3H/HeJ mouse model reveals the importance of T-cell activation via co-stimulation.

JP Sundberg1, KJ McElwee1,2, D Boggess1, K Silva1, LE King3, M Byrne4, and J Carroll4. The Jackson Laboratory, Bar Harbor, ME1; Currrent address: Phillipp University, Marburg, Germany2; Vanderbilt University and the Nashville VA Medical Centers, Nashville, TN3; and the Genetics Institute, Andover, MA, U.S.A.

Alopecia areata is an autoimmune disease that targets anagen hair follicles resulting in patchy to diffuse baldness. C3H/HeJ mice may develop spontaneous alopecia areata-like hair loss that closely resembles this human disease. Alopecia areata can also be induced in normal haired littermates using full thickness skin grafts. Since activated lymphocytes are postulated to play a role in this disease, this study focused on the activation of lymphocytes via co-stimulation as being important in onset and perpetuation of alopecia areata in mice. Transcript analysis using Affymetrix gene chips was done on RNA from skin of human alopecia totalis patients compared with normal age, sex, and biopsy site matched people. Similar studies were done on RNA from skin of mice with and without alopecia areata as well as sequentially after grafting alopecia areata affected skin or normal skin onto C3H/HeJ mice. Early upregulation of genes involved in lymphocyte activation and late upregulation of genes coding for viable chains of immunoglobulins were found. Using the inducible mouse model, alopecia areata could be blocked using monoclonal antibodies directed against either B7-1/B7-2 or mCTLA4Ig, supporting the lymphocyte co-stimulatory cascade as being important in early onset alopecia areata. Array technology has defined several inflammatory mechanisms involved in alopecia areata that could be targets for new treatment interventions.