Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris

• Type of Material: Article
• Authors: Edmund Lee, Rockefeller University; William L. Trepicchio, Millennium Pharmaceuticals, Inc.; Judith L. Oestreicher, Wyeth Research; Debra Pittman, Wyeth Research; Frank Wang, Rockefeller University; Francesca Chamian, Rockefeller University; Madhav Dhodapkar, Emory University; James G. Krueger, Rockefeller University
• Language: English
• Date: 2004-01-05
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2004, The Rockefeller University Press
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.20030451
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 199
• Issue: 1
• Start Page: 125
• End Page: 130
• Grant/Funding Information: J. Krueger and E. Lee were supported by National Institutes of Health (NIH) grants AI-49572, AI-49832, 1-K23-AR49815-01, and M01-RR00102.; M. Dhodapkar was supported by NIH grant CA 84512 and a Clinical Investigator Award from Damon Runyon Cancer Research Fund.
• Keywords: IL-12; DISTINCT; Medicine, Research & Experimental; gene expression; Th1 cells; ENDOTHELIAL-CELLS; CYTOTOXIC T-LYMPHOCYTE; IL-23; SUBUNIT; cytokines; DENDRITIC CELLS; dendritic cell; CYTOKINE; INFLAMMATION; Immunology; ACTIVATION; Research & Experimental Medicine; Science & Technology; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology; Biology, Genetics; Health Sciences, Immunology

Abstract

Psoriasis is a type I-deviated disease characterized by the presence of interferon (IFN)-γ 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.