Development immunomodulative drug based on the recognition mechanism of viral B-DNA.

基于病毒B-DNA识别机制开发免疫调节药物。

• 批准号: 20200074
• 负责人: TAKESHITA Fumihiko
• 金额: $ 20.88万
• 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 on Innovative Areas (Research a proposed research project)
• 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-20200074/
• 关键词: 感染防御; 分子; 基礎医学; ヒストン; 自然免疫; 免疫調節薬

Previous our data have discovered the novel H2B function to recognize non-chromosomal double stranded DNA (dsDNA), and induce antiviral innate immune response. In current research, we constructed the fusion protein, named as N'-CARD, by fusion of IPS-1 fragment with H2B fragment, and found that N'-CARD induced type I interferons (Type I IFNs) production. In addition, nuclear DNA helicase II was identified as N'-CARD associated molecules, and was indispensable for N'-CARD-mediated innate immune response. Furthermore, N'-CARD fused to protein transduction domain (N'-CARD-PTD) is a candidate of novel adjuvant. Therefore, current research revealed H2B-sensing machinery of cytoplasmic dsDNA as well as novel adjuvant candidate for vaccine development.

我们的前期工作发现了H2 B识别非染色体双链DNA（dsDNA）的新功能，并诱导抗病毒天然免疫应答。本研究将IPS-1基因片段与H2 B基因片段融合，构建了N '-CARD融合蛋白，发现N'-CARD可诱导I型干扰素（Type I IFN）的产生。此外，核DNA解旋酶II被鉴定为N '-CARD相关分子，并且在N'-CARD介导的先天免疫应答中是不可缺少的。此外，N '-CARD融合蛋白转导结构域（N'-CARD-PTD）是一种新型佐剂的候选者。因此，目前的研究揭示了胞质dsDNA的H2 B敏感机制以及用于疫苗开发的新佐剂候选物。

项目成果

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

Tryptophan aspartate-containing coat protein (CORO1A) suppresses Toll-like receptor signalling in Mycobacterium leprae infection.

含有色氨酸天冬氨酸的外壳蛋白 (CORO1A) 抑制麻风分枝杆菌感染中的 Toll 样受体信号传导。

• 发表时间: 2009
• 期刊: Clin Exp Immunol 156
• 作者: Tanigawa;K.;K.Suzuki;H.Kimura;F.Takeshita;H.Wu;T.Akama;A.Kawashima;N.Ishii.
• 通讯作者: N.Ishii.

Extrachromosomal Histone H2B Mediates Innate Antiviral Immune Responses Induced by Intracellular Double-Stranded DNA

• DOI: 10.1128/jvi.01339-09
• 发表时间: 2010-01-15
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Kobiyama, Kouji;Takeshita, Fumihiko;Suzuki, Koichi
• 通讯作者: Suzuki, Koichi

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

染色体外ヒストンH2Bを介する二本鎖DNA認識機構の利用

利用染色体外组蛋白 H2B 介导的双链 DNA 识别机制

• 发表时间: 2011