Small interference RNA modulation of IL-10 in human monocyte-derived dendritic cells enhances the Th1 response.
RNA interference technology has been used to modulate dendritic cell (DC) function by targeting the expression of genes such as IL-12 and NF-kappa B. In this paper, we demonstrate that transfection of DC with IL-10-specific double strands of small interference RNA (siRNA) resulted in potent suppression of IL-10 gene expression without inducing DC apoptosis or blocking DC maturation. Inhibition of IL-10 by siRNA was accompanied by increased CD40 expression and IL-12 production after maturation, which endowed DC with the ability to significantly enhance allogeneic T cell proliferation. IL-10 siRNA transfection did not affect MHC class II, CD86, CD83, or CD54 expression in mature DC. To further test the ability of IL-10 siRNA-treated DC to induce a T cell response, naive CD4 T cells were stimulated by autologous DC pulsed with KLH. The results indicated that IL-10 siRNA-transfected DC enhanced Th1 responses by increasing IFN-gamma and decreasing IL-4 production. These findings suggest the potential for a novel immunotherapeutic strategy of using IL-10 siRNA-transfected antigen-presenting cells as vaccine delivery agents to boost the Th1 response against pathogens and tumors that are controlled by Th1 immunity.
Liu
Gentao
G
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, 90048, USA.
Ng
Hiushan
H
Akasaki
Yasuharu
Y
Yuan
Xiangpeng
X
Ehtesham
Moneeb
M
Yin
Dong
D
Black
Keith L
KL
Yu
John S
JS
D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D034622:RNA Interference / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D014162:Transfection
D019013:CD40 Antigens; D034741:RNA, Small Interfering; D016753:Interleukin-10; D018664:Interleukin-12