The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online 30 October 2006 doi:10.1084/jem.20060244
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 12, 2577-2587
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ARTICLE

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

Jason R. Chan1, Wendy Blumenschein2, Erin Murphy2, Caroline Diveu1, Maria Wiekowski3, Susan Abbondanzo3, Linda Lucian1, Richard Geissler4, Scott Brodie4, Alexa B. Kimball5, Daniel M. Gorman2, Kathleen Smith2, Rene de Waal Malefyt1, Robert A. Kastelein1, Terrill K. McClanahan2, and Edward P. Bowman1

1 Discovery Research and 2 Experimental Pathology and Pharmacology, Schering-Plough Biopharma (formerly DNAX Research, Inc.), Palo Alto, CA 94304
3 Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033
4 Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, NJ 07848
5 Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305

CORRESPONDENCE Edward P. Bowman: eddie.bowman{at}spcorp.com

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.

A.B. Kimball's present address is Massachusetts General and Brigham and Women's Hospitals, Harvard Medical School, Boston, MA 02114.

Abbreviations used: EM, electron micrograph; K16, keratin 16; KGF, keratinocyte growth factor 1.


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