Fascin is involved in the antigen presentation activity of mature dendritic cells.
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-ss and increased by the addition TNF-alpha 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.
Al-Alwan
M M
MM
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Rowden
G
G
Lee
T D
TD
West
K A
KA
D000199:Actins / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D012867:Skin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000199:Actins; D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051940:B7-2 Antigen; D002352:Carrier Proteins; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C020324:fascin