In Psoriasis Lesional Skin the Type I Interferon Signaling Pathway Is Activated, whereas Interferon-α Sensitivity Is Unaltered
The Journal of Investigative Dermatology , Volume 122 - Issue 1 p. 51- 60
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.
|Inflammation, Interferon regulatory factor, Interferon-α, Keratinocytes|
|The Journal of Investigative Dermatology|
|Organisation||Department of Immunology|
van der Fits, L, van der Wel, L.I, Laman, J.D, Prens, E.P, & Verschuren, M.C.M. (2004). In Psoriasis Lesional Skin the Type I Interferon Signaling Pathway Is Activated, whereas Interferon-α Sensitivity Is Unaltered. The Journal of Investigative Dermatology, 122(1), 51–60. doi:10.1046/j.0022-202X.2003.22113.x