The Journal of Experimental Medicine
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Published 5 January 2004. doi:10.1084/jem.20030451
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 125-130
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Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris

Edmund Lee1, William L. Trepicchio3, Judith L. Oestreicher4, Debra Pittman4, Frank Wang1, Francesca Chamian1, Madhav Dhodapkar2 and James G. Krueger1

1 Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10021
2 Laboratory for Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
3 Millennium Pharmaceuticals, Clinical Research-Pharmacogenomics, Cambridge, MA 02139
4 Wyeth, Andover, MA 01810

Address correspondence to Edmund Lee or James G. Krueger, Laboratory for Investigative Dermatology, The Rockefeller University Hospital, P.O. Box 178, 1230 York Avenue, New York, NY 10021. Phone: (212) 327-7017; Fax: (212) 327-8232; email: leee{at}rockefeller.edu

Psoriasis is a type I–deviated disease characterized by the presence of interferon (IFN)-{gamma} and multiple IFN-related inflammatory genes in lesions. Because interleukin (IL)-23 is now recognized to play a role in the recruitment of inflammatory cells in a T helper cell (Th)1-mediated disease, we examined psoriasis skin lesions for production of this newly described cytokine. IL-23 is composed of two subunits: a unique p19 subunit and a p40 subunit shared with IL-12. We found a reliable increase in p19 mRNA by quantitative reverse transcription polymerase chain reaction in lesional skin compared with nonlesional skin (22.3-fold increase; P = 0.001). The p40 subunit, shared by IL-12 and IL-23, increased by 11.6-fold compared with nonlesional skin (P = 0.003), but the IL-12 p35 subunit was not increased in lesional skin. IL-23 was expressed mainly by dermal cells and increased p40 immunoreactivity was visualized in large dermal cells in the lesions. Cell isolation experiments from psoriatic tissue showed strong expression of p19 mRNA in cells expressing monocyte (CD14+ CD11c+ CD83-) and mature dendritic cell (DC) markers (CD14- CD11c+ CD83+), whereas in culture, the mRNAs for p40 and p19 were strongly up-regulated in stimulated monocytes and monocyte-derived DCs, persisting in the latter for much longer periods than IL-12. Our data suggest that IL-23 is playing a more dominant role than IL-12 in psoriasis, a Th1 type of human inflammatory disease.

Key Words: cytokines • gene expression • dendritic cell • IL-23 • Th1 cells

Abbreviation used in this paper: hARP, human acidic ribosomal protein gene.

The online version of this article contains supplemental material.


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