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Low Expression of the IL-23/Th17 Pathway in Atopic Dermatitis Compared to Psoriasis¹

Emma Guttman-Yassky^*, Michelle A. Lowes^*, Judilyn Fuentes-Duculan^*, Lisa C. Zaba^*, Irma Cardinale^*, Kristine E. Nograles^*, Artemis Khatcherian^*, Inna Novitskaya^*, John A. Carucci, Reuven Bergman and James G. Krueger^2,*

^* Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10021; The Section of Mohs Micrographic and Dermatologic Surgery, Weill-Cornell Medical College of Cornell, New York, NY 10065; and Department of Dermatology, Rambam Medical Center and the Technion, Haifa, Israel

The classical Th1/Th2 paradigm previously defining atopic dermatitis (AD) and psoriasis has recently been challenged with the discovery of Th17 T cells that synthesize IL-17 and IL-22. Although it is becoming evident that many Th1 diseases including psoriasis have a strong IL-17 signal, the importance of Th17 T cells in AD is still unclear. We examined and compared skin biopsies from AD and psoriasis patients by gene microarray, RT-PCR, immunohistochemistry, and immunofluorescence. We found a reduced genomic expression of IL-23, IL-17, and IFN- in AD compared with psoriasis. To define the effects of IL-17 and IL-22 on keratinocytes, we performed gene array studies with cytokine-treated keratinocytes. We found lipocalin 2 and numerous other innate defense genes to be selectively induced in keratinocytes by IL-17. IFN- had no effect on antimicrobial gene-expression in keratinocytes. In AD skin lesions, protein and mRNA expression of lipocalin 2 and other innate defense genes (hBD2, elafin, LL37) were reduced compared with psoriasis. Although AD has been framed by the Th1/Th2 paradigm as a Th2 polar disease, we present evidence that the IL-23/Th17 axis is largely absent, perhaps accounting for recurrent skin infections in this disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ J.G.K. is supported by a Clinical Translational Science Award UL1 RR024143 from the National Center for Research Resources at the National Institutes of Health. M.A.L. is the recipient of National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant K23 AR052404–01A1. L.Z. is supported by National Institutes of Health Medical Scientist Training Program Grant GM07739.

² Address correspondence and reprint requests to Dr. James G. Krueger, Laboratory for Investigative Dermatology, Box 178, Rockefeller University, York Avenue, New York, NY 10021. E-mail address: jgk{at}rockefeller.edu

³ Abbreviations used in this paper: AD, atopic dermatitis; LCN2, lipocalin 2; hARP, human acidic ribosomal protein; DC, dendritic cell; SLPI, secretory leukocyte proteinase inhibitor.

⁴ The online version of this article contains supplementary material.

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