The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions
The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions
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DOI：
10.1016/j.immuni.2006.01.014
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发表时间：
2006-03-01
期刊：
影响因子：
32.4
通讯作者：
Fontoura, BMA
中科院分区：
文献类型：
--
作者：
Faria, AMC;Levay, A;Fontoura, BMA
Nup 98和Nup 96是核转运机制的组成部分，由干扰素（IFN）诱导。Nup 98是mRNA输出途径的组成部分，其被病毒靶向并由IFN调节。然而，Nup 96在IFN相关机制中的作用尚未确定。为了研究Nup 96在体内的功能，我们产生了表达低水平Nup 96的Nup 86（+/-）小鼠，因为Nup 96（-/-）小鼠是致死的。Nup 96（+/-）小鼠表现出免疫系统的选择性改变，这导致IFN α和IFN γ介导的MHC I诱导和IFN γ诱导的MHC II、ICAM-1和其他蛋白质的下调和受损。依赖于MHC功能的TCR α β +和CD 4 + T细胞的频率在NUP 96（+/-）小鼠中降低。在免疫后，Nup 96（+/-）小鼠显示受损的抗原呈递和T细胞增殖。Nup 96（+/-）细胞和小鼠对病毒感染高度敏感，证明了Nup 96在先天性和适应性免疫中的作用。
Nup98 and Nup96 are components of the nuclear transport machinery and are induced by interferons (IFN). Nup98 is a constituent of an mRNA export pathway that is targeted by viruses and regulated by IFN. However, the role of Nup96 in IFN-related mechanisms has not been established. To investigate the function of Nup96 in vivo, we generated Nup86(+/-) mice that express low levels of Nup96, as Nup96(-/-) mice are lethal. The Nup96(+/-) mice presented selective alterations of the immune system, which resulted in downregulation and impaired IFN alpha- and gamma-mediated induction of MHC I and IFN gamma induction of MHC II, ICAM-1, and other proteins. Frequency of TCR alpha beta+ and CD4+ T cells, which depends on MHC function, is reduced in NUP96(+/-) mice. Upon immunization, Nup96(+/-) mice showed impaired antigen presentation and T cell proliferation. Nup96(+/-) cells and mice were highly susceptible to viral infection, demonstrating a role for Nup96 in innate and adaptive immunity.