Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 5, Pages 2216-2223Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1402989
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [Sonderforschungsbereich 685]
- DFG [RO 764/14-1]
- Wilhelm-Sander Stiftung Grant [2012.056.1/2]
- Deutsche Krebshilfe Grant [110664]
- Eberhard Karls University Tubingen Interdisziplinares Zentrum fur Klinische Forschung Verbundprojekt
- Bundesministerium fur Bildung und Forschung Grant [0315079]
Ask authors/readers for more resources
Small interfering RNA (siRNA)-based therapies allow targeted correction of molecular defects in distinct cell populations. Although efficient in multiple cell populations, dendritic cells (DCs) seem to resist siRNA delivery. Using fluorescence labeling and radiolabeling, we show that cholesterol modification enables siRNA uptake by DCs in vitro and in vivo. Delivery of cholesterol-modified p40 siRNA selectively abolished p40 transcription and suppressed TLR-triggered p40 production by DCs. During immunization with peptide in CFA, cholesterol-modified p40 siRNA generated p40-deficient, IL-10-producing DCs that prevented IL-17/Th17 and IFN-gamma/Th1 responses. Only cholesterol-modified p40-siRNA established protective immunity against experimental autoimmune encephalomyelitis and suppressed IFN-gamma and IL-17 expression by CNS-infiltrating mononuclear cells without inducing regulatory T cells. Because cholesterol-modified siRNA can thus modify selected DC functions in vivo, it is intriguing for targeted immune therapy of allergic, autoimmune, or neoplastic diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available