Journal of Molecular Medicine

, Volume 87, Issue 5, pp 523–536

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 Sabat
Original Article

DOI: 10.1007/s00109-009-0457-0

Cite this article as:
Wolk, K., Haugen, H.S., Xu, W. et al. J Mol Med (2009) 87: 523. doi:10.1007/s00109-009-0457-0
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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.

Keywords

Skin Inflammation Cytokine receptors Cytokines Interleukins Chemokines 

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
  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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