TY - JOUR

T1 - Increased sensitivity to interferon-alpha in psoriatic T cells

AU - Eriksen, Karsten Wessel

AU - Lovato, Paola

AU - Skov, Lone

AU - Krejsgaard, Thorbjørn

AU - Kaltoft, Keld

AU - Geisler, Carsten

AU - Ødum, Niels

N1 - Keywords: Apoptosis; Humans; Interferon Type II; Interferon-alpha; Promoter Regions (Genetics); Psoriasis; STAT4 Transcription Factor; Signal Transduction; T-Lymphocytes

PY - 2005

Y1 - 2005

N2 - Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT responses to other cytokines were not changed in psoriasis. In conclusion, we provide evidence that psoriatic T cells have an increased sensitivity to IFN-alpha. Thus, our data suggest that increased IFN-alpha signaling is involved in the pathogenesis of psoriasis.

AB - Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT responses to other cytokines were not changed in psoriasis. In conclusion, we provide evidence that psoriatic T cells have an increased sensitivity to IFN-alpha. Thus, our data suggest that increased IFN-alpha signaling is involved in the pathogenesis of psoriasis.

U2 - 10.1111/j.0022-202X.2005.23864.x

DO - 10.1111/j.0022-202X.2005.23864.x

M3 - Journal article

C2 - 16297193

VL - 125

SP - 936

EP - 944

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 5

ER -