Elucidation of the mechanism underlying core histone-mediated antiviral innate immune response

阐明核心组蛋白介导的抗病毒先天免疫反应的机制

• 批准号: 20590477
• 负责人: TAKESHITA Fumihiko
• 金额: $ 3.16万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590477/
• 关键词: 感染防御; ウイルス学; 基礎医学; ヒストン; 自然免疫; 免疫調節薬

Previous our research has clarified that H2B could sense viral double stranded DNA (dsDNA), and induce antiviral innate immune response. The goal of current research is to elucidate molecular mechanism of H2B-mediated recognition of cytoplasmic DNA.The results showed that extranuclear H2B interacts with IPS-1 upon sensing cytoplasmic DNA. We also identified the novel adaptor molecule, named as CIAO, to connect H2B with IPS-1, and showed that H2B-CIAO-IPS-1 complex has an important role to induce type I IFNs upon antiviral innate immune response. Furthermore, chimera protein N'-CARD, that is constructed by fusion of H2B fragment to IPS-1 fragment, could induce strong type I IFNs production, suggesting that H2B-CIAO-IPS-1 complex could be useful target to develop the novel immunomodulating drugs.

本课题组前期的研究已经阐明H2 B可以感知病毒双链DNA（dsDNA），并诱导抗病毒的天然免疫应答。本研究的目的是阐明H2 B介导的细胞质DNA识别的分子机制。我们还鉴定了连接H2 B和IPS-1的新型接头分子，命名为CIAO，并表明H2 B-CIAO-IPS-1复合物在诱导抗病毒天然免疫应答的I型IFN中具有重要作用。此外，H2 B片段与IPS-1片段融合构建的嵌合蛋白N '-CARD可诱导I型IFN的产生，提示H2 B-CIAO-IPS-1复合物可能成为开发新型免疫调节药物的有效靶点。

项目成果

IPS-1変異体による新規自然免疫活性化メカニズムの解析および免疫調節薬への応用

IPS-1突变体新型先天免疫激活机制分析及其在免疫调节药物中的应用

• 发表时间: 2008
• 作者: 小檜山康司;武下文彦;石井健;鈴木幸一;奥田研爾
• 通讯作者: 奥田研爾

Immunogenicity of Whole-Parasite Vaccines against Plasmodium falciparum Involves Malarial Hemozoin and Host TLR9

• DOI: 10.1016/j.chom.2009.12.003
• 发表时间: 2010-01-21
• 期刊: CELL HOST & MICROBE
• 影响因子: 30.3
• 作者: Coban, Cevayir;Igari, Yoshikatsu;Akira, Shizuo
• 通讯作者: Akira, Shizuo

Modulation of intracellular signaling using protein transduction technology.

使用蛋白质转导技术调节细胞内信号传导。

• 发表时间: 2010
• 期刊: Critical Reviews in Immunology
• 影响因子: 1.3
• 作者: Kobiyama K;Jounai N;Ishii KJ;Horii T;Suzuki K;Ryo A;Takeshita F.
• 通讯作者: Takeshita F.

C/EBPδ and STAT-1 Are Required for TLR8 Transcriptional Activity

• DOI: 10.1074/jbc.m110.133884
• 发表时间: 2010-11-05
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Zannetti, Claudia;Bonnay, Francois;Hasan, Uzma A.
• 通讯作者: Hasan, Uzma A.

NLRP4 negatively regulates autophagic process through an association with Beclin1.

NLRP4 通过与 Beclin1 的关联来负向调节自噬过程。

• 发表时间: 2010
• 作者: 今井由美子;(他2);Nao Jounai
• 通讯作者: Nao Jounai