Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA.
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 (N(1)-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.
Kruse
M
M
Department of Dermatology, University Erlangen-Nürnberg, D-91054 Erlangen, Germany.
Rosorius
O
O
Krätzer
F
F
Bevec
D
D
Kuhnt
C
C
Steinkasserer
A
A
Schuler
G
G
Hauber
J
J
D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation; D000097574:Eukaryotic Translation Initiation Factor 5A; D000097802:CD83 Antigen
D015703:Antigens, CD; D006147:Guanine; D007136:Immunoglobulins; D008239:Lysine; D008562:Membrane Glycoproteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; D000097802:CD83 Antigen; C100667:N(1)-guanyl-1,7-diaminoheptane; C100028:hypusine