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IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis

2006; Rockefeller University Press; Volume: 203; Issue: 12 Linguagem: Inglês

10.1084/jem.20060244

1540-9538

Jason R. Chan, Wendy M. Blumenschein, Erin Murphy, Caroline Diveu, Maria Wiekowski, Susan J. Abbondanzo, Linda Lucian, Richard Geissler, Scott J. Brodie, Alexa B. Kimball, Daniel M. Gorman, Kathleen M. Smith, René de Waal Malefyt, Robert A. Kastelein, Terrill K. McClanahan, Edward P. Bowman,

Cytokine Signaling Pathways and Interactions

Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor-dependent, but IL-17A-independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.