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* Department of Medicine, Division of Rheumatology, Departments of
Microbiology and Immunology and
Surgery, University of Western Ontario, London, Ontario, Canada;
MultiOrgan Transplant Program, London Health Science Center,
¶ Immunology and Transplantation, Lawson Health Research Institute, London, Ontario, Canada;
|| John P. Robarts Research Institute, London, Ontario, Canada; and
# ToleroTech Inc., London, Ontario, Canada
RNA interference is a mechanism of posttranscriptional gene silencing that functions in most eukaryotic cells, including human and mouse. Specific gene silencing is mediated by short strands of duplex RNA of 
21 nt in length (termed small interfering RNA or siRNA) that target the cognate mRNA sequence for degradation. We demonstrate here that RNAi can be used for immune modulation by targeting dendritic cell (DC) gene expression. Transfection of DC with siRNA specific for the IL-12 p35 gene resulted in potent suppression of gene expression and blockade of bioactive IL-12 p70 production without affecting unrelated genes or cellular viability. Inhibition of IL-12 was associated with increased IL-10 production, which endowed the DC with the ability to stimulate production of Th2 cytokines from allogenic T cells in vitro. Furthermore, siRNA-silenced DC lacking IL-12 production were poor allostimulators in MLR. IL-12-silenced and KLH-pulsed DC polarized the immune response toward a Th2 cytokine profile in an Ag-specific manner. These data are the first to demonstrate that RNA interference is a potent and specific tool for modulating DC-mediated immune responses.
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