Model of induction of a Th1-cytokine response by proteinase 3 (PR3). In WG, expression of PR3 in the extracellular space is increased. PR3 stimulates the expression of PAR-2 on iDCs. PR3 activates PAR-2 resulting in maturation of DCs, as indicated by expression of CD80, CD83, CD86, and HLA-DR. These PR3-maturated DCs stimulate CD4⁺ T cells to generate increased expression of interferon-γ (IFN-γ). Expression of IFN-γ favors the development of a granulomatous inflammation as seen in WG. Hypothetically, chronic T-cell activation by PR3-maturated DCs may finally promote the development of B cells toward ANCA-producing plasma cells.