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

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 alpha- and gamma-mediated induction of MHC I and IFNgamma induction of MHC II, ICAM-1, and other proteins. Frequency of TCRalphabeta+ 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.

• Authors: 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
• Journal: Immunity (Immunity) Vol. 24 Issue 3 Pg. 295-304 (Mar 2006) ISSN: 1074-7613 [Print] United States
• PMID: 16546098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• B7-2 Antigen
• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II
• Nuclear Pore Complex Proteins
• RNA, Messenger
• nuclear pore complex protein 96
• Intercellular Adhesion Molecule-1
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• B-Lymphocytes (physiology)
• B7-2 Antigen (analysis)
• Cell Nucleus (pathology)
• Histocompatibility Antigens Class I (analysis)
• Histocompatibility Antigens Class II (analysis)
• Immunity, Innate
• Intercellular Adhesion Molecule-1 (analysis)
• Interferon-gamma (pharmacology)
• Interleukin-4 (biosynthesis)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Nuclear Pore Complex Proteins (physiology)
• RNA, Messenger (analysis)
• T-Lymphocytes (physiology)