Crow Mary K, Kirou Kyriakos A, Wohlgemuth Jay
Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, 535 East 70th Street, New York, NY, USA.
Autoimmunity. 2003 Dec;36(8):481-90. doi: 10.1080/08916930310001625952.
Altered regulation of interferon-alpha (IFNalpha) in systemic lupus erythematosus (SLE) was first demonstrated nearly 25 years ago. However, only recently has due attention been directed towards the central role of this cytokine family in SLE. Several laboratories have used large-scale microarray technology to study global gene expression patterns in heterogeneous populations of peripheral blood cells from lupus patients and control subjects. The results of these studies demonstrate that IFN-regulated genes are among the most significantly overexpressed in SLE mononuclear cells. In view of the protean effects of IFNs on immune system function, increased activity of IFNs may account for many of the immune system alterations that characterize SLE and contribute to autoimmunity. Definition of the nature of the major IFNs, or other factors, that drive the IFN-regulated gene expression signature noted in SLE is an important area for investigation that may lead to new approaches to targeted therapy of SLE.
近25年前首次证明了系统性红斑狼疮(SLE)中α干扰素(IFNα)调节异常。然而,直到最近才开始充分关注这个细胞因子家族在SLE中的核心作用。几个实验室已使用大规模微阵列技术来研究狼疮患者和对照受试者外周血细胞异质群体中的整体基因表达模式。这些研究结果表明,IFN调节基因在SLE单核细胞中是最显著过度表达的基因之一。鉴于IFN对免疫系统功能的多种影响,IFN活性增加可能是SLE特征性免疫系统改变的原因,并导致自身免疫。确定驱动SLE中IFN调节基因表达特征的主要IFN或其他因素的性质是一个重要的研究领域,可能会带来SLE靶向治疗的新方法。