The Journal of Experimental Medicine
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Published online 1 May 2000.
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© The Rockefeller University Press, 0022-1007/2000/5/1581/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 9, May 1, 2000 1581-1590

Original Article

Inhibition of Cd83 Cell Surface Expression during Dendritic Cell Maturation by Interference with Nuclear Export of Cd83 mRNA

Monika Krusea, Olaf Rosoriusb, Friedrich Krätzerb, Dorian Bevecc, Christine Kuhnta, Alexander Steinkasserera, Gerold Schulera, and Joachim Hauberb

a Department of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
b Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany
c Department of Immunology, Novartis Research Institute, A-1235 Vienna, Austria
Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany.49-9131-85-2210149-9131-85-26182

jmhauber{at}viro.med.uni-erlangen.de

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.

Key Words: dendritic cells • CD83 • hypusine • eIF-5A • nuclear export

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.

© 2000 The Rockefeller University Press


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