F16 THE ROLE OF FAS AND FAS LIGAND IN ALOPECIA AREATA OF C3H/HeJ MICE

¹Freyschmidt-Paul P., ¹McElwee K.J., ²Botchkarev V., ³Sundberg J.P., ¹Happle R., ¹Hoffmann R. ¹Dept. of Dermatology, Philipp University, Marburg, Germany; ²Dept. of Dermatology, Boston Universtiy School of Medicine, USA; ³The Jackson Laboratory, Bar Harbor, USA.

Interaction of Fas ligand (FasL) with its receptor Fas leads to apoptosis of the Fas-expressing cell. Fas has been shown to be expressed on hair follicles and FasL on cells of perifollicular infiltrates in alopecia areata (AA) patients. Fas-deficient lpr and Fas ligand-deficient gld mice are relatively resistant to experimental induction of T-cell mediated autoimmune diseases such as diabetes mellitus or autoimmune encephalitis. Because AA is regarded as a T-cell mediated autoimmune disease, we addressed the question whether lpr and gld mice are resistant to the induction of AA.

We used the C3H/HeJ mouse model with induction of alopecia areata in unaffected mice by grafting of lesional alopecia areata mouse skin. Lesional AA skin was grafted onto C3H.MRL-Faslpr mice, C3H/HeJ-Faslgld mice and onto genetically normal C3H/HeJ mice as a control. Control mice developed AA within 10 weeks, whereas C3H.MRL-Faslpr and C3H/HeJ-Faslgld mice did not develop AA within 20 weeks after grafting. Immunohistochemical analysis revealed a peri- and intrafollicular lymphocytic infiltrate of CD4⁺ and CD8⁺ T-cells around anagen hair follicles and an aberrant expression of MHC class I and II on hair follicle epithelium in control mice, whereas in C3H.MRL-Faslpr and C3H/HeJ-Faslgld mice there was no perifollicular infiltrate and no aberrant expression of MHC class I and II of anagen hair follicles.

Our results show that C3H.MRL-Faslpr and C3H/HeJ-Faslgld mice are resistant to induction of AA. These findings suggest an important pathogenetic role of the Fas-Fas ligand system in AA.