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

J Mol Med (Berl). 2009 May;87(5):523-36. doi: 10.1007/s00109-009-0457-0. Epub 2009 Mar 30.


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)-gamma 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-gamma and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / metabolism
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Epidermis / drug effects*
  • Epidermis / metabolism
  • Epidermis / pathology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / pharmacology*
  • Interleukin-17 / pharmacology*
  • Interleukins / genetics
  • Interleukins / metabolism
  • Interleukins / pharmacology*
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Psoriasis / genetics
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology


  • Chemokines
  • Interleukin-17
  • Interleukins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • interleukin 20
  • interleukin-22