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

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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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    Faria, A. M. C., Levay, A., Wang, Y., Kamphorst, A. O., Rosa, M. L. P., Nussenzveig, D. R., Balkan, W., Chook, Y. M., Levy, D. E., & Fontoura, B. M. A. (2006). The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions. Immunity, 24(3), 295-304. https://doi.org/10.1016/j.immuni.2006.01.014