Dendritic cells (DCs), nature's adjuvant, must mature to sensitize T cells. However, although the maturation process is essential, it is not yet fully understood at the molecular level. In this study, we investigated the course of expression of the unique hypusine-containing protein eukaryotic initiation factor 5A (eIF-5A), which is part of a particular RNA nuclear export pathway, during in vitro generation of human DCs. We show that eIF-5A expression is significantly upregulated during DC maturation. Furthermore, an inhibitor of the hypusine modification, GC7 (N1-guanyl-1,7-diaminoheptane), prevents CD83 surface expression by apparently interfering with nucleocytoplasmic translocation of the CD83 mRNA and, importantly, significantly inhibits DC-mediated T lymphocyte activation. The data presented suggest that CD83 mRNA is transported from the nucleus to the cytoplasm via a specific nuclear export pathway and that hypusine formation appears to be essential for the maturation of functional DCs. Therefore, pharmacological interference with hypusine formation may provide a new possibility to modulate DC function.
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1 May 2000
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May 01 2000
Inhibition of Cd83 Cell Surface Expression during Dendritic Cell Maturation by Interference with Nuclear Export of Cd83 mRNA
Monika Kruse,
Monika Kruse
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
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Olaf Rosorius,
Olaf Rosorius
bInstitute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
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Friedrich Krätzer,
Friedrich Krätzer
bInstitute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
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Dorian Bevec,
Dorian Bevec
cDepartment of Immunology, Novartis Research Institute, A-1235 Vienna, Austria
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Christine Kuhnt,
Christine Kuhnt
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
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Alexander Steinkasserer,
Alexander Steinkasserer
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
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Gerold Schuler,
Gerold Schuler
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
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Joachim Hauber
Joachim Hauber
bInstitute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
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Monika Kruse
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
Olaf Rosorius
bInstitute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
Friedrich Krätzer
bInstitute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
Dorian Bevec
cDepartment of Immunology, Novartis Research Institute, A-1235 Vienna, Austria
Christine Kuhnt
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
Alexander Steinkasserer
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
Gerold Schuler
aDepartment of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
Joachim Hauber
bInstitute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
M. Kruse and O. Rosorius contributed equally to this study.
D. Bevec's current address is Axxima Pharmaceuticals AG, Am Klopferspitz 19, D-82152 Martinsried, Germany.
Abbreviations used in this paper: AREs, AU-rich elements; DCs, dendritic cells; eIF-5A, eukaryotic initiation factor 5A; ERG, early response gene; hnRNPs, heterogeneous nuclear ribonucleoproteins.
Received:
September 10 1999
Revision Requested:
March 08 2000
Accepted:
March 13 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (9): 1581–1590.
Article history
Received:
September 10 1999
Revision Requested:
March 08 2000
Accepted:
March 13 2000
Citation
Monika Kruse, Olaf Rosorius, Friedrich Krätzer, Dorian Bevec, Christine Kuhnt, Alexander Steinkasserer, Gerold Schuler, Joachim Hauber; Inhibition of Cd83 Cell Surface Expression during Dendritic Cell Maturation by Interference with Nuclear Export of Cd83 mRNA. J Exp Med 1 May 2000; 191 (9): 1581–1590. doi: https://doi.org/10.1084/jem.191.9.1581
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