Dendritic cell activation mechanism by Toll-like receptors

Toll样受体的树突状细胞激活机制

• 批准号: 14570280
• 负责人: KAISHO Tsuneyasu
• 金额: $ 2.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570280/
• 关键词: Gene targeting; Dendritic cell; Innate immunity; Adaptive immunity; Toll-like receptor; Lipopolysaccharides; CpG DNA; アダプター分子; LPS; 2本鎖RNA; シグナル伝達; MyD88

Dendritic cells (DCs) are critical for linking innate and adaptive immunity. This function is mainly mediated by a group of type I transmembrane proteins, Toll-like receptors (TLRs). In this study, function and signaling mechanisms of TLRs have been clarified as follows.1. TLR7 can recognize antiviral chemical compounds and virus-derived single stranded RNAs. TLR7 ligand can difirentially activate DC subsets. Furthermore, a TLR9 ligand, CpG DNA, can also stimulate DCs in a subset-dependent manner.2. LPS can activate DCs through production of interferon-beta (IFN-β). There are five intracytoplasmic adapters that can associate with TLRs, including MyD88,TIRAP/MAL, TRIF, TRAM, and SARM. This IFN-β induction does not depend on MyD88 or TIRAP/MAL but on TRIF and TRAM. Furthermore, TLR4 signaling can enhance Th1 cell supporting ability of DCs through MyD88 and can also activate Th2 cell supporting ability in a MyD88-independent manner.3. Double stranded RNAS can activate TLR3 signaling through TRIF, but not through TRAM or MyD88.

树突状细胞（DC）对于连接先天免疫和适应性免疫至关重要，该功能主要由一组 I 型跨膜蛋白 Toll 样受体（TLR）介导。在这项研究中，TLR 的功能和信号传导机制已被阐明。 1. TLR7 可以识别抗病毒化合物，并且病毒来源的单链 RNA 可以差异性地激活 DC 亚群。 CpG DNA 也可以以子集依赖性方式刺激 DC。 2. LPS 可以通过产生干扰素-β (IFN-β) 来激活 DC。 有五种胞质内接头可以与 TLR 结合，包括 MyD88、TIRAP/MAL、 TRIF、TRAM 和 SARM。这种 IFN-β 诱导不依赖于 MyD88 或 TIRAP/MAL，而是依赖于 TRIF 和 TRAM。此外，TLR4 信号传导可以增强。 DCs通过MyD88支持Th1细胞的能力，并且还能够以不依赖MyD88的方式激活Th2细胞的支持能力。3.双链RNAS可以通过TRIF激活TLR3信号，但不能通过TRAM或MyD88激活TLR3信号。

项目成果

S.S.Diebold, T.Kaisho, H.Hemmi, S.Akira, C.Reis e Sousa: "Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA."Science. 303. 1529-1531 (2004)

S.S.Diebold、T.Kaisho、H.Hemmi、S.Akira、C.Reis e Sousa：“通过 TLR7 介导的单链 RNA 识别产生先天抗病毒反应。”科学。

H.Hemmi, T.Kaisho, K.et al.: "The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets"J.Immunol. 170. 3059-3064 (2003)

H.Hemmi、T.Kaisho、K.et al.：“Toll 样受体 9、MyD88 和 DNA 依赖性蛋白激酶催化亚基在两种不同 CpG DNA 对树突状细胞亚群的影响中的作用”J.Immunol

T.Kaisho, et al.: "Endotoxin can induce MyD88-deficient dendritic cells to support Th2 cell differentiation"Int.Immunol.. 14. 695-700 (2002)

T.Kaisho 等人：“内毒素可以诱导 MyD88 缺陷的树突状细胞支持 Th2 细胞分化”Int.Immunol.. 14. 695-700 (2002)

T.Takeda, et al.: "Ann Rev Immunol"Annual Reviews. 335-376 (2003)

T.Takeda 等人：“Ann Rev Nutrition”年度评论。

T.Takeda, T.Kaisho, S.Akira: "Toll-like receptors."Ann Rev Immunol. 21. 335-376 (2003)

T.Takeda、T.Kaisho、S.Akira：“Toll 样受体”。Ann Rev Nutrition。