pathway licences them for TH1 priming via the protease-activated receptor-2 Wegener's autoantigen induces maturation of dendritic cells and

Abstract Autoantibodies to proteinase 3 (PR3) are involved in the pathogenesis of autoimmune-mediated vasculitis in Wegener`s granulomatosis (WG). To address the question how the autoantigen PR3 becomes target of adaptive immunity, we investigated the effect of PR3 on immature dendritic cells (iDCs) in patients with WG, healthy blood donors and patients with Crohn`s disease (CD), another granulomatous disease. PR3 induces phenotypic and functional maturation of a fraction of blood monocyte-derived iDCs. PR3-treated DCs express high levels of CD83, a DC-restricted marker of maturation, CD80 and CD86, and HLA-DR. Furthermore, they become fully competent antigen presenting cells and can induce stimulation of PR3-specific CD4 + T cells, which produce IFN-. PR3-maturated DCs derived γfrom WG patients induce a higher INF-γ response of PR3-specific CD4 + T cells as compared to patients with CD and healthy controls. The maturation of DC mediated through PR3 was inhibited by a serine protease inhibitor, by antibodies directed against the protease-activated receptor-2 (PAR-2) and by inhibition of phospholipase C, suggesting that the interactions of PR3 with PAR-2 are involved in the induction of DC maturation. Wegener`s autoantigen interacts with a “gateway” receptor (PAR-2) on iDCs