The karyopherin CRM1 is required for dendritic cell maturation.
Dendritic cells (DC) are the most potent antigen-presenting cells (APC) of the immune system and are specialized to activate T as well as B cell-dependent immune responses. Mature DC are characterized by expression of CD83, a surface molecule that has been postulated to be required for efficient DC activity. Here we show that Leptomycin B (LMB), a highly specific inhibitor of the nuclear export receptor CRM1, abrogates the ability of DC to stimulate T cells in an allogeneic mixed lymphocyte reaction. Interestingly, this effect correlates with down-regulation of CD83, CD80 and CD86 surface expression during DC maturation, whereas other investigated DC surface molecules, such as MHC class I and II molecules are not significantly affected. Analysis of RNA distribution reveals that particularly the stimulated expression of CD83 depended on a functional CRM1 export receptor. Taken together, the presented data show a critical involvement of the CRM1 transport receptor in DC maturation, most likely by enabling efficient nucleo-cytoplasmic translocation of specific mRNAs. Thus, interference with this pathway may provide new strategies to modulate DC function and, subsequently, DC-mediated immune responses.
Chemnitz
Jan
J
Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse 52, D-20251 Hamburg, Germany. jan.chemnitz@hpi.uni-hamburg.de
Turza
Nadine
N
Hauber
Ilona
I
Steinkasserer
Alexander
A
Hauber
Joachim
J
D015703:Antigens, CD / Q000096:biosynthesis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D028884:Karyopherins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009504:Neutrophils / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen
D015703:Antigens, CD; D005231:Fatty Acids, Unsaturated; D007136:Immunoglobulins; D028884:Karyopherins; D008562:Membrane Glycoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen; C038753:leptomycin B