Fascin is involved in the antigen presentation activity of mature dendritic cells

Maturation of dendritic cells (DC) is critical to their development into po tent APCs, Upon maturation, DC up-regulate the expression of MHC class II a s well as costimulatory and adhesion molecules, all of which are important in Ag presentation. In addition, they undergo structural changes characteri zed by the expression of numerous long dendrites. Fascin is an actin-bundli ng protein that has been reported to be important for the development of de ndrites, In this study, we evaluated fascin expression and function during DC maturation into potent APC, In vitro, treatment of bone marrow-derived D C (BM-DC) with GM-CSF resulted in increased levels of fascin expression. Th is increase correlated directly with an increase in MHC class II and B7-2 e xpression, Fascin expression was decreased by the addition of TGF-beta and increased by the addition TNF-alpha to the culture. These cytokines suppres s or enhance DC maturation, respectively, Increased levels of fascin expres sion 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 play s a significant role in the ability of DC to function as APC, This observat ion is the first evidence linking fascin-mediated dendrite formation with t he APC activity of DC.