Down-Regulation of TLR9 Expression Affects the Maturation and Function of Murine Bone Marrow-Derived Dendritic Cells Induced by CpG
Down-Regulation of TLR9 Expression Affects the Maturation and Function of Murine Bone Marrow-Derived Dendritic Cells Induced by CpG
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TLR9表达下调影响CpG诱导的小鼠骨髓源性树突状细胞的成熟和功能
DOI：
10.1038/cmi.2009.27
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发表时间：
2009-06-01
影响因子：
24.1
通讯作者：
Hou, Yayi
中科院分区：
文献类型：
--
作者：
Ma, Ling;Zhao, Guangfeng;Hou, Yayi
Toll样受体9（TLR 9）由树突状细胞（DC）在细胞内表达，并特异性识别未甲基化的CpG基序。TLR 9对CpG DNA的识别可以诱导DC成熟，随后是随后的免疫应答。在这里，RNA干扰（RNAi）被用于鉴定CpG DNA信号传导对DC功能的影响。结果显示，TLR 9基因特异性siRNA转染DCs后，能显著下调DCs TLR 9的表达。用TLR 9 siRNA转染的未成熟DC在暴露于CpG时不分化为成熟DC。TLR 9 siRNA处理的DC表达低水平的MHC II和CD 40，而不减少内吞作用。此外，TLR 9 siRNA转染的DC在淋巴细胞增殖试验中表现出降低的同种异体刺激能力，并通过降低IL-12 p70的产生来减弱Th 1应答。我们的研究结果表明，siRNA沉默TLR 9基因在DC中可能提供一个潜在的工具，研究TLR 9-CpG通路。
Toll-like receptor 9 (TLR9) is expressed intracellularly by dendritic cells (DCs) and specifically recognizes unmethylated CpG motif. Recognition of TLR9 to CpG DNA can induce DC maturation followed by the subsequent immune responses. Here, RNA interference (RNAi) was used to identify the effect of CpG DNA signaling on DC function. The results showed that transfection of DCs with siRNA specific for TLR9 gene significantly down-regulated TLR9 expression. Immature DCs transfected with TLR9 siRNA did not differentiate into mature DCs with exposure to CpG. TLR9 siRNA-treated DCs expressed low levels of MHC II and CD40 without reducing endocytosis. Furthermore, TLR9 siRNA-transfected DCs exhibited a decreased allostimulatory capacity in a lymphocyte proliferation assay and attenuated Th1 responses by decreasing IL-12p70 production. Our findings indicate that siRNA in silencing TLR9 gene in DCs may offer a potential tool to study the TLR9-CpG pathway.