L-07   THERAPEUTIC TRIALS OF ALOPECIA AREATA IN C3H/HEJ MICE

P. Freyschmidt-Paul Dept. of Dermatology, Philipp University, Marburg, Germany.

C3H/HeJ mice develop hair loss that shows clinical, histopathological and immunohistochemical features of human alopecia areata. This hair loss does not only develop spontaneously, but it can also be experimentally induced in unaffected C3H/HeJ mice or other histocompatible strains by grafting of AA-affected mouse skin. Therefore, C3H/HeJ mice with alopecia areata can be used I. to study the mechanisms of how current treatments of alopecia areata act, II. to study the efficacy and safety of new treatment forms in established alopecia areata and III. to assess the influence of various factors on the development of alopecia areata in order to prevent the onset of the disease. Using this mouse model we have shown that treatment of alopecia areata with a contact sensitizer acts by increasing the number of CD4+ cells and reducing the numbers of CD8+ cells in the skin. Future studies will help to identify the mechanisms by which CD4+ cells reduce the pathogenetic effects of CD8+ cells in alopecia areata. Therapeutic studies have shown that alopecia areata of C3H/HeJ mice can be treated with topical tacrolimus. Therefore topical tacrolimus should also be effective in human alopecia areata if a suitable vehicle can be developed that is able to carry tacrolimus down to the human hair bulb. Alopecia areata-induction studies have shown that the onset of alopecia areata can be inhibited by the injection of an anti-CD44v10 antibody in C3H/HeJ mice. Because this anti-CD44v10 antibody selectively inhibits homing of autoimmune or malignant lymphocytes to the skin, the application of such an antibody could also be useful to inhibit the onset of human AA. Other induction studies, using Fas- and FasL-deficient mice have shown, that the induction of apoptosis in the hair follicle by the Fas/FasL-system is crucially involved in the development of alopecia areata. Therefore modulation of the Fas/FasL-system in the hair follicle might be useful to prevent hair follicle damage in alopecia areata. Future studies using the C3H/HeJ mouse model may focus on the induction of tolerance or the possibilities of gene therapy to treat alopecia areata.