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,
,*,
Departments of
*
Microbiology and Immunology,
Pathology,
Medicine, and
Surgery, Dalhousie University, Halifax, Nova Scotia, Canada
Maturation of dendritic cells (DC) is critical to their development
into potent APCs. Upon maturation, DC up-regulate the expression of MHC
class II as well as costimulatory and adhesion molecules, all of which
are important in Ag presentation. In addition, they undergo structural
changes characterized by the expression of numerous long dendrites.
Fascin is an actin-bundling protein that has been reported to be
important for the development of dendrites. In this study, we evaluated
fascin expression and function during DC maturation into potent APC. In
vitro, treatment of bone marrow-derived DC (BM-DC) with GM-CSF resulted
in increased levels of fascin expression. This increase correlated
directly with an increase in MHC class II and B7-2 expression. Fascin
expression was decreased by the addition of TGF-
and increased by
the addition TNF-
to the culture. These cytokines suppress or
enhance DC maturation, respectively. Increased levels of fascin
expression were found to correlate with increased APC activity in a
one-way MLR. Specific inhibition of fascin expression, using antisense
oligonucleotides, markedly reduced this APC allostimulatory activity.
These data demonstrate that fascin expression correlates with DC
maturation into APC, and it plays a significant role in the ability of
DC to function as APC. This observation is the first evidence linking
fascin-mediated dendrite formation with the APC activity of
DC.
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