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Title: VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors
Authors: Dasgupta, Suryasarathi ×
Repesse, Yohann
Bayry, Jagadeesh
Navarrete, Ana-Maria
Wootla, Bharath
Delignat, Sandrine
Irinopoulou, Theano
Kamate, Caroline
Saint-Remy, Jean-Marie
Jacquemin, Marc
Lenting, Peter J
Borel-Derlon, Annie
Kaveri, Srinivas V
Lacroix-Desmazes, Sebastien #
Issue Date: 15-Jan-2007
Publisher: W.B. Saunders
Series Title: Blood vol:109 issue:2 pages:610-612
Abstract: Von Willebrand factor (VWF) is a chaperone molecule for procoagulant factor VIII (FVIII). Its role in the reduction of the immunogenicity of therapeutic FVIII in patients with hemophilia A has been evoked, but lacks clear cellular and molecular rational. Here, we demonstrate that VWF protects FVIII from being endocytosed by human dendritic cells (DCs) and subsequently presented to FVIII-specific T cells. The immunoprotective effect of VWF requires a physical interaction with FVIII, as the endocytosis of FVIII was significantly restored upon hindering the formation of the VWF-FVIII complex. Interestingly, VWF had no direct inhibitory effect either on the ability of DCs to present antigenic peptides, or on the activation potency of CD4+ T cells. We thus propose that VWF may reduce the immunogenicity of FVIII by preventing, upstream from the activation of immune effectors, the entry of FVIII in professional antigen presenting cells.
URI: 
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

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