The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions.
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.
Departamento de Bioquímica e Imunologia, Instituto the Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Ana M C
AM
Faria
Agata
A
Levay
Yaming
Y
Wang
Alice O
AO
Kamphorst
Magda L P
ML
Rosa
Daniel R
DR
Nussenzveig
Wayne
W
Balkan
Yuh Min
YM
Chook
David E
DE
Levy
Beatriz M A
BM
Fontoura
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D051940:B7-2 Antigen / Q000032:analysis; D002467:Cell Nucleus / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D028861:Nuclear Pore Complex Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology
D051940:B7-2 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; C119239:nuclear pore complex protein 96; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma