Targeting plasmocytoid dendritic cells with protein-based nanoparticles for the treatment of asthma
Martin F. Bachmann
Cytos Biotechnology AG,
Wagistrasse 25, CH-8952 Schlieren,
Switzerland
Abstract:
Allergen-specific T helper type 2 (Th2) responses are an important cause of allergic asthma. We have previously shown that protein-based nanoparticles loaded with a synthetic, DNA-based toll-like receptor 9 (TLR9) agonist (QbG10) are potent injectable drugs for the treatment of asthma. In humans, plasmacytoid dendritic cells (pDCs) are the only antigen-presenting cells expressing TLR9. To elucidate the mechanism of action of QbG10, we therefore studied the response of pDCs to QbG10. Since patients respond with strong antibody responses to the protein-based QbG10 nanoparticles, we also studied the influence of specific antibodies on the response of pDCs. Our results may be summarized as such. 1) QbG10 induces production of IFNa, shutting down the production of Th2 cytokines; 2) QbG10 induces ICOSL on pDCs, leading to the generation of regulatory T cells and a massive reduction in the production of pro-inflammatory cytokines. 3) Presence of specific antibodies strongly enhances the pharmacodynamic effects of QbG10. Hence, QbG10 controls asthma by inhibiting Th2 responses and by fostering the generation of regulatory T cells.
