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Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis¹

Leslie van der Fits^2,*,, Sabine Mourits^*,, Jane S. A. Voerman, Marius Kant^*,, Louis Boon, Jon D. Laman, Ferry Cornelissen^,, Anne-Marie Mus^,, Edwin Florencia^*,, Errol P. Prens^3,*, and Erik Lubberts^3,,

Departments of ^* Dermatology, Immunology, and Rheumatology, Erasmus Medical Center, Rotterdam, The Netherlands; and Bioceros BV, Utrecht, The Netherlands

Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4⁺ T cells, CD11c⁺ dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis.

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.S.A.V. and J.D.L. are supported by the Dutch MS Research Foundation. F.C., A.-M.M., and E.L. are supported by the Dutch Arthritis Foundation.

² Address correspondence and reprint requests to Dr. Leslie van der Fits, Department of Dermatology, Room T02-32, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail address: L.vanderfits{at}lumc.nl

³ E.P.P. and E.L. contributed equally to this work.

⁴ Abbreviations used in this paper: IMQ, imiquimod; DETC, -positive dendritic epidermal T cells; KO, knockout; LC, Langerhans cells; pDC, plasmacytoid dendritic cells; WT, wild type.

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				C. B. Salem, H. Hmouda, K. Bouraoui, F. O. Nestle, D. Kaplan, and J. Barker Psoriasis N. Engl. J. Med., October 22, 2009; 361(17): 1710 - 1710. [Full Text] [PDF]

				F. O. Nestle, D. H. Kaplan, and J. Barker Psoriasis N. Engl. J. Med., July 30, 2009; 361(5): 496 - 509. [Full Text] [PDF]