Prominent production of IL-20 by CD68+/CD11c+ Myeloid-derived cells in psoriasis: Gene regulation and cellular effects

Frank Wang, Edmund Lee, Michelle A. Lowes, Asifa S. Haider, Judilyn Fuentes-Duculan, Maria Veronica Abello, Francesca Chamian, Irma Cardinale, James G. Krueger

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72 Scopus citations

Abstract

We assessed expression of IL-20 and its receptors in psoriasis, given the recent implication of IL-20 in epidermal hyperplasia. Psoriatic lesional (LS) skin consistently expressed more IL-20 mRNA than nonlesional (NL) skin. Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68+/CD11c+ (myeloid-derived) dermal leukocytes. Because this contrasted with earlier reports of a keratinocyte source, we assessed IL-20 mRNA expression in a variety of cells in vitro, and confirmed a myeloid-derived cellular source (monocytes). Plastic adhesion, activation of β2 integrins, and incubation with tumor necrosis factor-α stimulated expression in these cells. IL-20 receptor (IL-20R)α and IL-20Rβ mRNA was decreased in LS versus NL skin, which also contrasted with earlier findings. To investigate the relationship between IL-20 and disease activity, we examined psoriasis patients treated with the CD2-targeted agent alefacept. In therapeutic responders, lesional IL-20 mRNA decreased to NL levels, suggesting that CD2+ leukocytes may proximally regulate IL-20. Finally, to assess IL-20 function, we used microarrays to screen IL-20-treated keratinocytes, which demonstrated upregulation of disease-related and IFN-γ-induced genes. Hence, IL-20 may influence inflammation through IFN-like effects. Together, these data indicate that IL-20 may be an important effector cytokine in psoriasis, and that its inhibition may represent a potential therapeutic target.

Original languageEnglish (US)
Pages (from-to)1590-1599
Number of pages10
JournalJournal of Investigative Dermatology
Volume126
Issue number7
DOIs
Publication statusPublished - Jul 1 2006

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Wang, F., Lee, E., Lowes, M. A., Haider, A. S., Fuentes-Duculan, J., Abello, M. V., ... Krueger, J. G. (2006). Prominent production of IL-20 by CD68+/CD11c+ Myeloid-derived cells in psoriasis: Gene regulation and cellular effects. Journal of Investigative Dermatology, 126(7), 1590-1599. https://doi.org/10.1038/sj.jid.5700310