Fas-deficient C3.MRL-Tnfrsf6(lpr) mice and Fas ligand-deficient C3H/HeJ-Tnfsf6(gld) mice are relatively resistant to the induction of alopecia areata by grafting of alopecia areata-affected skin from C3H/HeJ mice.
Alopecia areata is suspected to be a T cell-mediated autoimmune disease of the hair follicle, where Fas is expressed on hair follicles and Fas ligand on perifollicular infiltrates. To elucidate whether the Fas/Fas ligand pathway is of pathogenetic significance in alopecia areata, we investigated whether alopecia areata can be induced in Fas-deficient and Fas ligand-deficient mice and whether alopecia areata develops in Fas-deficient and Fas ligand-deficient skin. Therefore, we induced alopecia areata by grafting alopecia areata-affected C3H/HeJ mouse skin on to C3H/HeJ mice (control), on to Fas ligand-deficient C3H/HeJ-Tnfsf6(gld) mice or Fas-deficient C3.MRL-Tnfrsf6(lpr) mice. All control mice developed alopecia areata, whereas no Fas-deficient mice showed hair loss and two of seven Fas ligand-deficient mice developed only transitory, limited alopecia areata. Moreover, skin from C3H/HeJ mice (control), C3H/HeJ-Tnfsf6(gld) mice, and C3.MRL-Tnfrsf6(lpr) mice was grafted on to C3H/HeJ mice with extensive alopecia areata. Skin grafts from control mice developed hair loss, whereas Fas-deficient and Fas ligand-deficient skin grafts were spared from alopecia areata. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling and immunofluorescence studies revealed an increased number of apoptotic cells and expression of Fas on hair follicles as well as expression of Fas ligand on cells of the perifollicular infiltrate in C3H/HeJ mice with alopecia areata, whereas in Fas-deficient and Fas ligand-deficient mice apoptotic cells were virtually absent in hair follicles. The results suggest that the Fas/Fas ligand pathway plays an important pathogenetic role in alopecia areata.
Freyschmidt-Paul
Pia
P
Department of Dermatology, Philipp University, Marburg, Germany. freyschm@mailer.uni-marburg.de
McElwee
Kevin J
KJ
Botchkarev
Vladimir
V
Kissling
Sabine
S
Wenzel
Elke
E
Sundberg
John P
JP
Happle
Rudolf
R
Hoffmann
Rolf
R
D000506:Alopecia Areata / Q000209:etiology*; D000818:Animals; D017209:Apoptosis; D004198:Disease Susceptibility; D053222:Fas Ligand Protein; D018859:Hair Follicle / Q000503:physiopathology*; D006579:Heterozygote; D007249:Inflammation / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008815:Mice, Inbred Strains; D012867:Skin / Q000378:metabolism; D016038:Skin Transplantation; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor