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PubMed · 16400020

Fas pulls the trigger on psoriasis.

Amos Gilhar·Ron Yaniv·Bedia Assy·Sima Serafimovich·Yehuda Ullmann·Richard S Kalish
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Abstract

Fas/FasL signaling is best known for induction of apoptosis. However, there is an alternate pathway of Fas signaling that induces inflammatory cytokines, particularly tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. This pathway is prominent in cells that express high levels of anti-apoptotic molecules such as Bcl-xL. Because TNF-alpha is central to the pathogenesis of psoriasis and psoriatic epidermis has a low apoptotic index with high expression of Bcl-xL, we hypothesized that inflammatory Fas signaling mediates induction of psoriasis by activated lymphocytes. Noninvolved skin from psoriasis patients was grafted to beige-severe combined immunodeficiency mice, and psoriasis was induced by injection of FasL-positive autologous natural killer cells that were activated by IL-2. Induction of psoriasis was inhibited by injection of a blocking anti-Fas (ZB4) or anti-FasL (4A5) antibody on days 3 and 10 after natural killer cell injection. Anti-Fas monoclonal antibody significantly reduced cell proliferation (Ki-67) and epidermal thickness, with inhibition of epidermal expression of TNF-alpha, IL-15, HLA-DR, and ICAM-1. Fas/FasL signaling is an essential early event in the induction of psoriasis by activated lymphocytes and is necessary for induction of key inflammatory cytokines including TNF-alpha and IL-15.

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Adoptive TransferAnimalsFas Ligand ProteinHumansImmunohistochemistryKiller Cells, NaturalLymphocyte ActivationMembrane GlycoproteinsMiceMice, SCIDPsoriasisReverse Transcriptase Polymerase Chain ReactionSignal TransductionSkin TransplantationTumor Necrosis Factor-alphaTumor Necrosis Factorsfas ReceptorJournal Article

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Amos Gilhar, Ron Yaniv, Bedia Assy, Sima Serafimovich, Yehuda Ullmann, Richard S Kalish. 2006. Fas pulls the trigger on psoriasis.. https://doi.org/10.2353/ajpath.2006.041354

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