TY - JOUR
T1 - In Psoriasis Lesional Skin the Type I Interferon Signaling Pathway Is Activated, whereas Interferon-α Sensitivity Is Unaltered
AU - Van Der Fits, Leslie
AU - Van Der Wel, Leontine I.
AU - Laman, Jon D.
AU - Prens, Errol P.
AU - Verschuren, Martie C.M.
PY - 2004/1
Y1 - 2004/1
N2 - 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.
AB - 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.
KW - Inflammation
KW - Interferon regulatory factor
KW - Interferon-α
KW - Keratinocytes
UR - http://www.scopus.com/inward/record.url?scp=1642493842&partnerID=8YFLogxK
U2 - 10.1046/j.0022-202X.2003.22113.x
DO - 10.1046/j.0022-202X.2003.22113.x
M3 - Article
C2 - 14962089
AN - SCOPUS:1642493842
SN - 0022-202X
VL - 122
SP - 51
EP - 60
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 1
ER -