In Psoriasis Lesional Skin the Type I Interferon Signaling Pathway Is Activated, whereas Interferon-α Sensitivity Is Unaltered

Leslie Van Der Fits*, Leontine I. Van Der Wel, Jon D. Laman, Errol P. Prens, Martie C.M. Verschuren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

113 Citations (Scopus)
25 Downloads (Pure)

Abstract

The epidermal phenotype as observed in psoriatic skin results from inflammation and abnormal proliferation and terminal differentiation of keratinocytes. Mice deficient for interferon regulatory factor-2, a repressor of interferon signaling, display psoriasis-like skin inflammation. The development of this phenotype is strictly dependent on type I interferon (interferon-α/β) signaling. The aim of this study was to assess the involvement of interferon-α/β in the pathogenesis of human psoriasis. In psoriatic skin, we measured an increased expression of components that play central and crucial roles in interferon-α/β signal transduction. Culturing keratinocytes or healthy skin biopsies with recombinant interferon-α stimulated this signaling pathway; however, this did not induce the expression of markers that are generally used to define the psoriasis phenotype. Furthermore, skin from psoriasis patients responded identically to interferon-α stimulation, demonstrating that psoriatic skin does not have an aberrant sensitivity to type I interferon. We conclude that in psoriatic lesional skin the type I interferon signaling pathway is activated, despite an unaltered interferon-α sensitivity. Our data furthermore show that type I interferon, in contrast to interferon-γ, does not act directly on keratinocytes to induce a psoriatic phenotype. Thus, if the observed activated type I interferon signaling is indeed functionally involved in the pathogenesis of psoriasis, its contribution might be indirect, putatively involving other cell types besides keratinocytes.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalJournal of Investigative Dermatology
Volume122
Issue number1
DOIs
Publication statusPublished - Jan-2004
Externally publishedYes

Keywords

  • Inflammation
  • Interferon regulatory factor
  • Interferon-α
  • Keratinocytes

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