The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions

被引：83

作者：

Faria, AMC

Levay, A

Wang, Y

Kamphorst, AO

Rosa, MLP

Nussenzveig, DR

Balkan, W

Chook, YM

Levy, DE

Fontoura, BMA ^{[1
]}

机构：

[1] Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA

[2] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA

[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil

[4] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[5] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA

来源：

IMMUNITY | 2006年 / 24卷 / 03期

关键词：

D O I：

10.1016/j.immuni.2006.01.014

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：295 / 304

页数：10

共 45 条

[1] T cell homeostasis: Thymus regeneration and peripheral T cell restoration in mice with a reduced fraction of competent precursors [J].