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IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not

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Abstract

Psoriasis is a common chronic skin disease with a largely unknown pathogenesis. We demonstrate here that transgenic over-expression of interleukin (IL)-22 in mice resulted in neonatal mortality and psoriasis-like skin alterations including acanthosis and hypogranularity. This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes. The comparison of cytokines with hypothesized roles in psoriasis pathogenesis determined that neither interferon (IFN)-γ nor IL-17, but only IL-22 and, with lower potency, IL-20 caused psoriasis-like morphological changes in a three-dimensional human epidermis model. These changes were associated with inhibited keratinocyte terminal differentiation and with STAT3 upregulation. The IL-22 effect on differentiation-regulating genes was STAT3-dependent. In contrast to IL-22 and IL-20, IFN-γ and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-α potently induced diverse chemokines and additionally enhanced the expression of IL-22 receptor pathway elements and amplified some IL-22 effects. This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations.

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Acknowledgments

The authors would like to acknowledge B. Ketel, A. Buss, and Wendy Curtis for excellent technical assistance and E. Wallace for accurately proofreading the manuscript. Prof. J. Lademann is acknowledged for placing the Olympus microscope at our disposal. We also thank the German Ministry of Education and Research for the generous support.

Disclosure

H. S. Haugen, W. Xu, K. Waggie, and M. Anderson are stockholders of ZymoGenetics. Inc. K. Wolk was consultant for Merck Serono S. A. until July 2008.

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Authors and Affiliations

  1. Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Charitéplatz 1, 10117, Berlin, Germany

    Kerstin Wolk, Ellen Witte, Katrin Witte, Katarzyna Warszawska, Sandra Philipp & Robert Sabat

  2. ZymoGenetics, Inc., 1201 Eastlake Avenue East, Seattle, WA, 98102, USA

    Harald S. Haugen, Wenfeng Xu, Kim Waggie & Monica Anderson

  3. Merck Serono S.A., 9 Chemin des Mines, 1202, Geneva, Switzerland

    Elmar vom Baur & Caroline Johnson-Leger

  4. Institute of Medical Immunology, University Hospital Charité, Charitéplatz 1, 10117, Berlin, Germany

    Hans-Dieter Volk

  5. Department of Dermatology, University Hospital Charité, Charitéplatz 1, 10117, Berlin, Germany

    Wolfram Sterry

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  1. Kerstin Wolk
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  2. Harald S. Haugen
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  3. Wenfeng Xu
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  14. Robert Sabat
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Correspondence to Robert Sabat.

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Kerstin Wolk and Harald S. Haugen equally contributed to this work.

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Wolk, K., Haugen, H.S., Xu, W. et al. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not. J Mol Med 87, 523–536 (2009). https://doi.org/10.1007/s00109-009-0457-0

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  • DOI: https://doi.org/10.1007/s00109-009-0457-0

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