Immunomodulatory nanoparticles as adjuvants and allergen-delivery system to human dendritic cells: Implications for specific immunotherapy |
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| Authors: | Sissela Broos Kristina Lundberg Takami Akagi Koji Kadowaki Mitsuru Akashi Lennart Greiff Carl A.K. Borrebaeck Malin Lindstedt |
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| Affiliation: | 1. Department of Immunotechnology, Lund University, Lund, Sweden;2. Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka, Japan;3. Department of Otorhinolaryngology, Lund University Hospital, Lund, Sweden |
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| Abstract: | Novel adjuvants and antigen-delivery systems with immunomodulatory properties that shift the allergenic Th2 response towards a Th1 or regulatory T cell response are desired for allergen-specific immunotherapy. This study demonstrates that 200-nm sized biodegradable poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) are activators of human monocyte-derived dendritic cells (MoDCs). γ-PGA NPs are efficiently internalized by immature MoDCs and strongly stimulate production of chemokines and inflammatory cytokines as well as up-regulation of co-stimulatory molecules and immunomodulatory mediators involved in efficient T cell priming. Furthermore, MoDCs from allergic subjects stimulated in vitro with a mixture of γ-PGA NPs and extract of grass pollen allergen Phleum pratense (Phl p) augment allergen-specific IL-10 production and proliferation of autologous CD4+ memory T cells. Thus, γ-PGA NPs are promising as sophisticated adjuvants and allergen-delivery systems in allergen-specific immunotherapy. |
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| Keywords: | DC, dendritic cell MAPK, mitogen-activated protein kinase MoDC, monocyte-derived dendritic cell NF-κB, nuclear factor-kappa B NP, nanoparticle PmB, polymyxin B PBMC, peripheral blood mononuclear cell Phl p, Phleum pratense γ-PGA, poly(gamma-glutamic acid) SIT, specific immunotherapy TLR, toll-like receptor TNF, tumor necrosis factor Treg, regulatory T cell |
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