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Immunobiology. 2010 May;215(5):370-9. doi: 10.1016/j.imbio.2009.05.008. Epub 2009 Jul 9.

The karyopherin CRM1 is required for dendritic cell maturation.

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Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse 52, D-20251 Hamburg, Germany.


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.

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