Dendritic cell activation mechanisms by nucleic by nucleic acid immune adjuvants.

核酸免疫佐剂通过核酸激活树突状细胞的机制。

基本信息

批准号：
18590483
负责人：
KAISHO Tsuneyasu
金额：
$ 2.57万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590483/
关键词：
Dendritic cell Toll-like receptor immune adjuvant type I interferon plasmacytoid dendritic cell double-starnded RNA 樹状細胞サブセット

项目摘要

Dendritic cells (DCs) recognize a variety of nucleic acids through Toll-like receptors (TLRs) and produce proinflammatory cytokines or type I interferons (IFNs). In this study, we have analyzed the underlying molecular mechanisms on these DC functions. Among TLRs, TLR3, TLR7 and TLR9 are involved in nucleic acid recognition. One DC subset, plasmacytoid DC (pDC), expresses TLR7 and TLR9 exclusively among TLRs and produce a large amount of type I IFNs upon TLR7/9 stimulation. A serine threonine kinase, IkB kinase α (IKKα), is critically involved in type I IFN production from TLR7/9-stimulated pDC. IKKα functioned. through the association with and phosphorylation of a transcription factor, IRF-7, which was known to be critical for type I IFN production by TLR7/9 stimuli. We have further investigated the mechanism by which a double-stranded RNA, poly (A: U) activate DCs. Poly (I: C) is a well-known double-stranded RNA, which can activate DCs through TLR3 and a cytosolic sensor, RIG-Hike receptor (RLR), but it remained unknown how poly (A: U) activates DCs. Poly (A: U) activated pDC to produce type I IFN and IL-12p40 in a TLR7-dependent manner. Poly (A: U) also induced IL-12p40 from conventional DC (cDC) through TLR3 and TLR7. When injected with antigen (Ag) into mice, poly (A: U) could induce clonal expansion of and IFN-y production from Ag-specific CD8-positive T cells. TLR3 was mainly involved in these in vivo effects of poly (A: U). Thus, poly (A: U) can function as an immune adjuvant through TLR3 and TLR7.

树突状细胞 (DC) 通过 Toll 样受体 (TLR) 识别多种核酸并产生促炎细胞因子或 I 型干扰素 (IFN)。在本研究中，我们分析了这些 TLR 功能的潜在分子机制。 TLR3、TLR7 和 TLR9 参与核酸识别，一种 DC 亚群，浆细胞样 DC (pDC)，在 TLR 中专门表达 TLR7 和 TLR9，并产生大量。 TLR7/9 刺激后的 IkB 激酶 α (IKKα) 通过与 TLR7/9 刺激的 pDC 的关联和磷酸化发挥重要作用。因子 IRF-7，已知对 TLR7/9 刺激产生 I 型干扰素至关重要。我们进一步研究了双链 RNA、聚 (A: Poly (I: C) 是一种众所周知的双链 RNA，它可以通过 TLR3 和胞质传感器 RIG-Hike 受体 (RLR) 激活 DC，但目前尚不清楚 Poly (A: U) 是如何激活 DC 的。 Poly (A: U) 激活 pDC，以 TLR7 依赖性方式产生 I 型 IFN 和 IL-12p40，Poly (A: U) 还可从常规 DC 中诱导 IL-12p40。 (cDC) 通过 TLR3 和 TLR7 注射抗原 (Ag) 到小鼠体内时，Poly (A: U) 可以诱导 Ag 特异性 CD8 阳性 T 细胞的克隆扩增，并且 TLR3 主要参与这些细胞的产生。 Poly(A:U)的体内作用因此，Poly(A:U)可以通过TLR3和TLR7发挥免疫佐剂的作用。