062 Further confirmation of the involvement of Fas and Fas ligand in alopecia areata of C3H/HeJ mice

P Freyschmidt-Paul, KJ McElwee, V Botchkarev, JP Sundberg, R Happle, R Hoffmann. Dept. of Dermatology, Philipp University, Marburg, Germany; Dept. of Dermatology, Boston University School of Medicine, MA; USA, The Jackson Laboratory, Bar Harbor, ME, USA.

Alopecia areata develops spontaneously in 20% of C3H/HeJ mice and can also be experimentally induced by grafting of AA affected skin to normal haired C3H/HeJ mice or mice from other histocompatible strains in graft recipients. We have shown, that Fas-deficient C3H.MRL-Faslpr and Fas ligand-deficient C3H/HeJ-Faslgld mice are resistant to experimental induction of AA. Fas has been shown to be expressed on hair follicles and FasL on cells of perifollicular infiltrates in alopecia areata (AA) patients. These findings suggest an important pathogenetic role of the Fas-Fas ligand system in AA. To further confirm this pathogenetic role of the Fas-Fas ligand system in AA we adressed the question, whether skin of Fas-deficient C3H.MRL-Faslpr and Fas ligand-deficient C3H/HeJ-Faslgld mice is resistant to the development of alopecia areata. To answer this question, we grafted haired skin of C3H.MRL-Faslpr and C3H/HeJ-Faslgld mice and of normal C3H/HeJ mice as a control onto C3H/HeJ mice with widespread alopecia areata. Before grafting, the skin grafts were shaved. 8 weeks after grafting, skin grafts from C3H.MRL-Faslpr and C3H/HeJ-Faslgld mice showed dense and long hair growth within the bald alopecia areata skin of the recipients. By contrast, normal skin grafts were bald or showed only thin, short hairs, comparable to those which can be found in alopecia areata of C3H/HeJ mice. Our results show, that skin of Fas-deficient C3H.MRL-Faslpr and Fas ligand-deficient C3H/HeJ-Faslgld mice is resistant to the development of alopecia areata. Therefore we conclude, that Fas ligand and its receptor Fas play a crucial role in the development of alopecia areata.