IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis

Eur J Immunol. 2006 May;36(5):1309-23. doi: 10.1002/eji.200535503.


IL-22 is an IFN-IL-10 cytokine family member, which is produced by activated Th1 and NK cells and acts primarily on epithelial cells. Here we demonstrate that IL-22, in contrast to its relative IFN-gamma, regulates the expression of only a few genes in keratinocytes. This is due to varied signal transduction. Gene expressions regulated by IL-22 should enhance antimicrobial defense [psoriasin (S100A7), calgranulin A (S100A8), calgranulin B (S100A9)], inhibit cellular differentiation (e.g., profilaggrin, keratins 1 and 10, kallikrein 7), and increase cellular mobility [e.g., matrix metalloproteinease 1 (MMP1, collagenase 1), MMP3 (stromelysin 1), desmocollin 1]. In contrast, IFN-gamma favored the expression of MHC pathway molecules, adhesion molecules, cytokines, chemokines, and their receptors. The IL-22 effects were transcriptional and either independent of protein synthesis and secretion, or mediated by a secreted protein. Inflammatory conditions, but not keratinocyte differentiation, amplified the IL-22 effects. IL-22 application in mice enhanced cutaneous S100A9 and MMP1 expression. High IL-22 levels in psoriatic skin were associated with strongly up-regulated cutaneous S100A7, S100A8, S100A9, and MMP1 expression. Psoriatic patients showed strongly elevated IL-22 plasma levels, which correlated with the disease severity. Expression of IL-22 and IL-22-regulated genes was reduced by anti-psoriatic therapy. In summary, despite similarities, IFN-gamma primarily amplifies inflammation, while IL-22 may be important in the innate immunity and reorganization of epithelia.

MeSH terms

  • Animals
  • Calgranulin A / genetics
  • Calgranulin B / genetics
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Gene Expression Regulation*
  • Humans
  • Interferon-gamma / physiology
  • Interleukins / physiology*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Mice
  • Mice, Inbred BALB C
  • Psoriasis / etiology*


  • Calgranulin A
  • Calgranulin B
  • Interleukins
  • Interferon-gamma
  • Matrix Metalloproteinase 1
  • interleukin-22