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CpG RNA: identification of novel single-stranded RNA that stimulates human CD14+CD11c+ monocytes.

Sugiyama, T
Gürsel, Mayda
Takeshita, F
Coban, C
Conover, J
Kaisho, T
Akira, S
Klinman, DM
Ishii, KJ
Synthetic immunostimulatory nucleic acids such as CpG DNA are being harnessed therapeutically as vaccine adjuvants, anticancer or antiallergic agents. Efforts to identify nucleic acid-based agents capable of more specifically modulating the immune system are being developed. The current study identifies a novel class of single-stranded oligoribonucleotides (ORN) containing unmethylated CpG motifs and a poly(G) run at the 3 end (CpG ORN) that directly stimulate human CD14 CD11c monocytes but not dendritic cells or B cells. CpG ORN activate NF-B and p38 MAPK, resulting in IL-6 and IL-12 production and costimulatory molecule up-regulation but not IFN. Methylation of cytosine at the 5 portion in core CpG motif abrogates such activation. TLR3, 7, 8, or 9 alone did not confer response to CpG ORN, in contrast to previously reported respective nucleic acid ligands. These data suggest that CpG ORN represent a novel class of synthetic immunostimulatory nucleic acids with distinct target cells, receptors, and functions from that of previously known immunomodulatory nucleic acids.