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

Ana M C Faria, Agata Levay, Yaming Wang, Alice O. Kamphorst, Magda L P Rosa, Daniel R. Nussenzveig, Wayne Balkan, Yuh Min Chook, David E. Levy, Beatriz M A Fontoura

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

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 Nup96+/- 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 α- and γ-mediated induction of MHC I and IFNγ induction of MHC II, ICAM-1, and other proteins. Frequency of TCRαβ+ 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.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalImmunity
Volume24
Issue number3
DOIs
StatePublished - Mar 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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