Increased sensitivity to interferon-a in psoriatic T cells

被引:72
作者
Eriksen, KW
Lovato, P
Skov, L
Krejsgaard, T
Kaltoft, K
Geisler, C
Odum, N
机构
[1] Univ Copenhagen, IMMI, Dept Immunol, Inst Mol Biol & Physiol, DK-2200 Copenhagen, Denmark
[2] Gentofte Univ Hosp, Dept Dermatol, Copenhagen, Denmark
[3] Univ Aarhus, Inst Human Genet, Aarhus, Denmark
[4] Univ Copenhagen, Inst Med Microbiol & Immunol, DK-2200 Copenhagen, Denmark
关键词
cytokines; inflammation; signal transduction; skin; T lymphocytes;
D O I
10.1111/j.0022-202X.2005.23864.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:936 / 944
页数:9
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