CpG RNA: Identification of Novel Single-Stranded RNA That Stimulates Human CD14+CD11c+ Monocytes
CpG RNA: Identification of Novel Single-Stranded RNA That Stimulates Human CD14+CD11c+ Monocytes
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DOI：
10.4049/jimmunol.174.4.2273
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发表时间：
2005-02
期刊：
影响因子：
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通讯作者：
T. Sugiyama;M. Gursel;F. Takeshita;C. Coban;J. Conover;T. Kaisho;S. Akira;D. Klinman;K. Ishii
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文献类型：
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作者：
T. Sugiyama;M. Gursel;F. Takeshita;C. Coban;J. Conover;T. Kaisho;S. Akira;D. Klinman;K. Ishii
合成的免疫刺激核酸如CpG DNA在治疗上被用作疫苗佐剂、抗癌剂或抗过敏剂。正在努力鉴定能够更特异性地调节免疫系统的基于核酸的试剂。目前的研究鉴定了一类新的单链寡核苷酸（ORN），其含有未甲基化的CpG基序和在3 '端的聚（G）运行（CpG ORN），其直接刺激人CD 14 + CD 11 c+单核细胞，但不刺激树突状细胞或B细胞。CpG ORN激活NF-κB和p38 MAPK，导致IL-6和IL-12的产生和共刺激分子的上调，但不激活IFNα。核心CpG基序5′端胞嘧啶的甲基化消除了这种激活。与先前报道的相应核酸配体相反，单独的TLR 3、7、8或9不赋予对CpG ORN的应答。这些数据表明，CpG ORN代表了一类新的合成免疫刺激核酸，其具有与先前已知的免疫调节核酸不同的靶细胞、受体和功能。
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-κB and p38 MAPK, resulting in IL-6 and IL-12 production and costimulatory molecule up-regulation but not IFNα. 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.