The Nucleoporin Nup96 Is Required for Proper Expression of Interferon-Regulated Proteins and Functions

• Published in: Immunity (Cambridge, Mass.) Vol. 24; no. 3; pp. 295 - 304
• Main Authors: Faria, Ana M.C., Levay, Agata, Wang, Yaming, Kamphorst, Alice O., Rosa, Magda L.P., Nussenzveig, Daniel R., Balkan, Wayne, Chook, Yuh Min, Levy, David E., Fontoura, Beatriz M.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2006; Elsevier Limited
• Subjects: Animals; B-Lymphocytes - physiology; B7-2 Antigen - analysis; Biomedical research; Cell Nucleus - pathology; Flow cytometry; Genes; Grants; Histocompatibility Antigens Class I - analysis; Histocompatibility Antigens Class II - analysis; Immunity, Innate; Intercellular Adhesion Molecule-1 - analysis; Interferon-gamma - pharmacology; Interleukin-4 - biosynthesis; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Nuclear Pore Complex Proteins - physiology; Proteins; RNA, Messenger - analysis; Software; T-Lymphocytes - physiology; Viral infections
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2006.01.014

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.