Increased sensitivity to interferon-alpha in psoriatic T cells.
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.
Eriksen
Karsten Wessel
KW
Institute of Molecular Biology and Physiology, Department of Immunology, University of Copenhagen, Copenhagen, Denmark.
Lovato
Paola
P
Skov
Lone
L
Krejsgaard
Thorbjørn
T
Kaltoft
Keld
K
Geisler
Carsten
C
Ødum
Niels
N
D017209:Apoptosis; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000276:immunology*; D050797:STAT4 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D016898:Interferon-alpha; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D007371:Interferon-gamma