Fas pulls the trigger on psoriasis

Area of Science:

• Immunodermatology
• Molecular Biology
• Cell Signaling

Background:

• Fas/FasL signaling traditionally induces apoptosis but can also trigger inflammatory cytokines, including tumor necrosis factor (TNF)-alpha.
• This inflammatory pathway is active in cells with high Bcl-xL, a feature of psoriatic epidermis which has low apoptosis.
• TNF-alpha is a key factor in psoriasis pathogenesis.

Purpose of the Study:

• To investigate the hypothesis that inflammatory Fas signaling, mediated by activated lymphocytes, induces psoriasis.
• To explore the role of Fas/FasL signaling in the early induction of psoriasis.

Main Methods:

• Grafting noninvolved skin from psoriasis patients onto immunodeficient mice.
• Inducing psoriasis via injection of activated, FasL-positive autologous natural killer (NK) cells.
• Administering blocking anti-Fas (ZB4) or anti-FasL (4A5) antibodies to assess inhibition of psoriasis induction.

Main Results:

• Psoriasis induction was significantly inhibited by anti-Fas and anti-FasL antibodies.
• Anti-Fas antibody treatment reduced epidermal cell proliferation (Ki-67), epidermal thickness, and expression of TNF-alpha, IL-15, HLA-DR, and ICAM-1.
• Fas/FasL signaling is essential for inducing key inflammatory cytokines like TNF-alpha and IL-15 in this psoriasis model.

Conclusions:

• Fas/FasL signaling is a critical early event in lymphocyte-induced psoriasis.
• This pathway is necessary for the induction of crucial inflammatory cytokines that drive psoriasis.
• Targeting Fas/FasL signaling offers a potential therapeutic strategy for psoriasis.