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-alpha/beta) signaling. The aim of this study was to assess the involvement of
interferon-alpha/beta in the pathogenesis of human
psoriasis. In psoriatic skin, we measured an increased expression of components that play central and crucial roles in
interferon-alpha/beta signal transduction. Culturing keratinocytes or healthy skin biopsies with recombinant
interferon-alpha 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-alpha 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-alpha sensitivity. Our data furthermore show that
type I interferon, in contrast to
interferon-gamma, 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.