Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 203, Issue 12, Pages 2577-2587Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20060244
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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.
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