Fas-mediated cell death in toxic epidermal necrolysis and graft-versus-host disease: potential for therapeutic inhibition.
Death receptors are a growing family of transmembrane proteins which can detect the presence of specific extracellular death signals and rapidly trigger cellular destruction by apoptosis. The best studied to date is Fas (CD95). Expression and signalling by Fas and its ligand (FasL, CD95L) is a tightly regulated process essential for key physiological functions in a variety of organs, including the maintenance of immune homoeostasis. Recently, strong evidence has shown that dysregulation of Fas expression and/or signalling contributes to the pathogenesis of toxic epidermal necrolysis and acute graft-versus-host disease. With these new developments, strategies for modulating the function of Fas signalling have emerged and opened up novel therapeutic possibilities. Specific blockade of Fas, for example with intravenous immunoglobulin preparations containing specific anti-Fas antibodies, has shown great promise in the treatment of toxic epidermal necrolysis and may also be useful in the treatment of acute graft-versus-host disease. Further developments in this field may have important clinical implications for the treatment of such diseases.
French
L E
LE
Department of Dermatology, Geneva University Medical School.
Tschopp
J
J
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D006086:Graft vs Host Disease / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D006801:Humans; D013262:Stevens-Johnson Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor