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Journal of Molecular Medicine

, Volume 87, Issue 5, pp 523–536 | Cite as

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

  • Kerstin Wolk
  • Harald S. Haugen
  • Wenfeng Xu
  • Ellen Witte
  • Kim Waggie
  • Monica Anderson
  • Elmar vom Baur
  • Katrin Witte
  • Katarzyna Warszawska
  • Sandra Philipp
  • Caroline Johnson-Leger
  • Hans-Dieter Volk
  • Wolfram Sterry
  • Robert SabatEmail author
Original Article

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.

Keywords

Skin Inflammation Cytokine receptors Cytokines Interleukins Chemokines 

Notes

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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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Kerstin Wolk
    • 1
  • Harald S. Haugen
    • 2
  • Wenfeng Xu
    • 2
  • Ellen Witte
    • 1
  • Kim Waggie
    • 2
  • Monica Anderson
    • 2
  • Elmar vom Baur
    • 3
  • Katrin Witte
    • 1
  • Katarzyna Warszawska
    • 1
  • Sandra Philipp
    • 1
  • Caroline Johnson-Leger
    • 3
  • Hans-Dieter Volk
    • 4
  • Wolfram Sterry
    • 5
  • Robert Sabat
    • 1
    Email author
  1. 1.Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical ImmunologyUniversity Hospital CharitéBerlinGermany
  2. 2.ZymoGenetics, Inc.SeattleUSA
  3. 3.Merck Serono S.A.GenevaSwitzerland
  4. 4.Institute of Medical ImmunologyUniversity Hospital CharitéBerlinGermany
  5. 5.Department of DermatologyUniversity Hospital CharitéBerlinGermany

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