Fas/Fas ligand-mediated apoptosis of murine Langerhans cells

Epidermal Langerhans cells (LC) are potent antigen-presenting cells (APC), that play a crucial role in initiating cutaneous immune responses. The Fas/Fas ligand pathway has been implicated as an important cellular pathway in the regulation of peripheral immunity. The morphologic, functional and phenotypic characteristics of LC are becoming well-characterized. However, the mechanisms involved in eliminating LC are poorly understood. In this report, we demonstrated that murine epidermal LC constitutively express the Fas antigen (CD95) and the expression was up-regulated by the addition of IFN-gamma in cultures. Interestingly, epidermal LC underwent apoptosis by the addition of both recombinant soluble Fas ligand (FasL) and IFN-gamma, but not by FasL alone. These results suggest that LC may acquire the susceptibility to Fas-mediated apoptosis through up-regulation of the Fas expression by IFN-gamma derived from activated T cells and that the elimination of LC may be important for preventing excess cutaneous inflammatory diseases.