Increased sensitivity to interferon-a in psoriatic T cells
Increased sensitivity to interferon-a in psoriatic T cells
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DOI：
10.1111/j.0022-202x.2005.23864.x
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发表时间：
2005-11-01
影响因子：
6.5
通讯作者：
Odum, N
中科院分区：
文献类型：
--
作者：
Eriksen, KW;Lovato, P;Odum, N
银屑病是一种以表皮增生异常为特征的慢性炎症性皮肤病。一些研究表明，皮肤浸润性活化T细胞和细胞因子在疾病的发生和维持中起关键作用。干扰素(IFN)- α在宿主防御感染中起着重要作用，但最近的数据也表明IFN- α与牛皮癣有关。因此，ifn - α在一些患者中诱导或加重银屑病，缺乏ifn - α / β信号转录衰减因子的小鼠自发发展为以CD8（+）浸润T细胞为特征的银屑病样炎症性皮肤病。因此，在这项研究中，我们研究了从银屑病患者受病皮肤中分离的T细胞中的ifn - α信号。我们发现，与来自非银屑病供者皮肤的浸润性T细胞相比，银屑病T细胞在信号转导和转录激活因子（STAT）激活水平上对ifn - α的反应增加并延长。功能上，ifn - α信号的增加导致STAT4与ifn - γ启动子的结合增加，ifn - γ产生增加，并抑制T细胞生长。相比之下，在牛皮癣中，STAT对其他细胞因子的反应没有改变。总之，我们提供的证据表明银屑病T细胞对ifn - α的敏感性增加。因此，我们的数据表明ifn - α信号的增加与牛皮癣的发病机制有关。
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.