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

Author:

Kruse Monika1,Rosorius Olaf2,Krätzer Friedrich2,Bevec Dorian3,Kuhnt Christine1,Steinkasserer Alexander1,Schuler Gerold1,Hauber Joachim2

Affiliation:

1. Department of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany

2. Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany

3. Department of Immunology, Novartis Research Institute, A-1235 Vienna, Austria

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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