VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors
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 #
Blood vol:109 issue:2 pages:610-612
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.