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。

• 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

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）识别各种核酸，并产生促炎性细胞因子或I型干扰素（IFNS）。在这项研究中，我们分析了这些DC功能的基本分子机制。在TLR中，TLR3，TLR7和TLR9参与了核酸识别。一个DC子集，浆细胞类动物DC（PDC），仅在TLR中表达TLR7和TLR9，并在TLR7/9刺激下产生大量的I型IFN。丝氨酸苏氨酸激酶IKB激酶α（IKKα）与TLR7/9刺激的PDC产生I型IFN产生。 IKKα功能。通过与转录因子IRF-7的关联和磷酸化，该转录因子对TLR7/9刺激的I型IFN产生至关重要。我们进一步研究了双链RNA poly（a：u）激活DC的机制。 poly（i：c）是一种众所周知的双链RNA，可以通过TLR3和胞质传感器，RIG-HIKE受体（RLR）激活DC，但它仍然未知如何激活DC。 Poly（A：U）激活的PDC以TLR7依赖性方式产生I型IFN和IL-12P40。 poly（a：u）还通过TLR3和TLR7从常规DC（CDC）诱导IL-12P40。当将抗原（Ag）注射到小鼠中时，Poly（a：u）可以诱导Ag特异性CD8阳性T细胞的克隆膨胀和IFN-Y产生。 TLR3主要参与poly（a：u）的体内效应。那就是poly（a：u）可以通过TLR3和TLR7充当免疫辅助。

项目成果

PDLIM2-mediated termination of transcription factor NF-kB activation by intranuclear sequestration and degradation fo the p65 subunit.

PDLIM2 介导的通过核内隔离和 p65 亚基降解来终止转录因子 NF-kB 的激活。

• 发表时间: 2007
• 期刊: Nature Immunol. 8(6)
• 作者: T. Tanaka;S. Uematsu;M. Nakahira;T. Tanaka
• 通讯作者: T. Tanaka

Toll-like receptor signaling is impaired in dendritic cells from patients with X-linked agammagloblinemia.

X 连锁无丙种球蛋白血症患者的树突状细胞中 Toll 样受体信号传导受损。

• 发表时间: 2008
• 期刊: Clin. Immunol. 126
• 作者: T.;Sato;T.;Chiba;S.;Ohno;K.;Kohu;M.;Satake;S.;Habu;T. Sugiyama;H. Taneichi
• 通讯作者: H. Taneichi

RHEUMATOLOGY FOURTH EDITION

风湿病学第四版

• 发表时间: 2008
• 作者: Matsushita M;et al.;S.A. Ha;T. Kaisho;田中 貴志;星野 克明;植松 智;T. Kaisho;T. Kaisho;T. Kaisho;改正 恒康;T. Kaisho;T. Kaisho;改正 恒康;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho
• 通讯作者: T. Kaisho

Critical involvement of IκB kinase-α in TLR7/9-induced type I IFN production.

IκB 激酶-α 在 TLR7/9 诱导的 I 型 IFN 产生中发挥重要作用。

• 发表时间: 2007
• 作者: Matsushita M;et al.;S.A. Ha;T. Kaisho;田中 貴志;星野 克明;植松 智;T. Kaisho;T. Kaisho;T. Kaisho;改正 恒康;T. Kaisho;T. Kaisho;改正 恒康;T. Kaisho;T. Kaisho;T. Kaisho
• 通讯作者: T. Kaisho

Critical involvement of IkB kinase-αin TLR7/9-induced type I IFN production.

IkB 激酶-α 在 TLR7/9 诱导的 I 型 IFN 产生中发挥重要作用。

• 发表时间: 2007
• 作者: Matsushita M;et al.;S.A. Ha;T. Kaisho;田中 貴志;星野 克明;植松 智;T. Kaisho;T. Kaisho;T. Kaisho;改正 恒康;T. Kaisho;T. Kaisho;改正 恒康;T. Kaisho;T. Kaisho;T. Kaisho;T. Kaisho
• 通讯作者: T. Kaisho