Cutting Edge: Bradykinin Induces IL-12 Production by Dendritic Cells: A Danger Signal That Drives Th1 Polarization

Abstract

Dendritic cells play a major role in the induction of both innate and acquired immune responses against patho genic invaders. These cells are also able to sense endoge nous activation signals liberated by injured tissues even in the absence of infection. In the present work, we demon strate that kinins mobilize dendritic cells to produce IL-12 through activation of the B2 bradykinin receptor subtype and that bradykinin-induced IL-12 responses are tightly regulated both by angiotensin-converting enzyme, a ki nin-degrading peptidase, and by endogenous IL-10. Using a mouse model of allergic inflammation, we further show that addition of bradykinin to OVA during immuniza tion results in decreased eosinophil infiltration on Ag chal lenge. The latter effect was demonstrated to be due to IL 12-driven skewing of Ag-specific T cell responses to a type 1 cytokine profile. Our data thus indicate that kinin pep tides can serve as danger signals that trigger dendritic cells to produce IL-12 through activation of B2 bradykinin receptors.