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免疫细胞中三重基序蛋白的I型干扰素依赖性和非依赖性表达。

Type I interferon-dependent and -independent expression of tripartite motif proteins in immune cells.

作者信息

Rajsbaum Ricardo, Stoye Jonathan P, O'Garra Anne

机构信息

Division of Immunoregulation, National Institute for Medical Research, London, UK.

出版信息

Eur J Immunol. 2008 Mar;38(3):619-30. doi: 10.1002/eji.200737916.

Abstract

The tripartite motif (TRIM) proteins are important in a variety of cellular functions additional to anti-viral activity. We systematically analysed mRNA expression of representative TRIM molecules in mouse macrophages, myeloid and plasmacytoid dendritic cells, and a selection of CD4(+) T cell subsets. We defined four clusters of TRIM genes based on their selective expression in these cells. The first group of TRIM genes was preferentially expressed in CD4(+) T cells and contained the COS-FN3 motif previously shown to be involved in protein interactions. Additional TRIM genes were identified that showed up-regulation in macrophages and dendritic cells upon influenza virus infection in a type I IFN-dependent manner, suggesting that they have anti-viral activity. In support of this notion, a subset of these TRIM molecules mapped to mouse chromosome 7, syntenic to human chromosome 11, where TRIM family members such as TRIM5, shown to have anti-viral activity, are localized. A distinct group of TRIM was constitutively expressed in plasmacytoid dendritic cells independently of viral infection or signalling through the type I IFN receptor. Our findings on expression and regulation of TRIM genes in cells of the immune system that have different effector functions in innate and adaptive immune responses, may provide leads for determining functions of this diverse family of molecules.

摘要

三联基序(TRIM)蛋白在多种细胞功能中发挥重要作用,不仅仅局限于抗病毒活性。我们系统分析了小鼠巨噬细胞、髓样和浆细胞样树突状细胞以及部分CD4(+) T细胞亚群中代表性TRIM分子的mRNA表达情况。基于这些细胞中的选择性表达,我们定义了四类TRIM基因簇。第一类TRIM基因在CD4(+) T细胞中优先表达,且包含先前已证明参与蛋白质相互作用的COS-FN3基序。我们还鉴定出了其他TRIM基因,它们在甲型流感病毒感染后,以I型干扰素依赖的方式在巨噬细胞和树突状细胞中上调表达,这表明它们具有抗病毒活性。支持这一观点的是,这些TRIM分子中的一部分定位于小鼠7号染色体,与人类11号染色体同线,而具有抗病毒活性的TRIM家族成员如TRIM5就定位在人类11号染色体上。有一类独特的TRIM在浆细胞样树突状细胞中持续表达,不受病毒感染或通过I型干扰素受体的信号传导影响。我们关于TRIM基因在免疫系统细胞中的表达和调控的研究结果,这些细胞在先天性和适应性免疫反应中具有不同的效应功能,可能为确定这个多样的分子家族的功能提供线索。

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