Developmental research on dendritic cell-based immunotherapy against chronic hepatitis C and hepatocellular carcinoma

基于树突状细胞的慢性丙型肝炎和肝细胞癌免疫治疗的进展研究

• 批准号: 19590765
• 负责人: KANTO Tatsuya
• 金额: $ 3万
• 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: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19590765/
• 关键词: 樹状細胞; C型肝炎; Toll様受容体; インターフェロンα; リバビリン; HCVプロテアーゼ阻害剤; Type III IFN; RIG-I

In hepatitis C virus (HCV) infection, it is well known that the impaired function of dendritic cells (DC) is critically involved in the development of liver disease as well as resistance to anti-viral therapy, such as a combination of peg-interferon-a and ribavirin. We demonstrated in this research project that myeloid DC (MDC) are functionally impaired in the production of type-I IFN and IL-12 in response to Toll-like receptor (TLR) signaling, of which is partly due to reduced expression of TRIF and TRAF6 adaptor molecules. In addition, the treatment of MDC with HCV NS3/4A protease inhibitor restored MDC of stimulatory capacity for CD4+ T cells. Therefore, we demonstrate that MDC could be served as a therapeutic target in order to enhance anti-HCV immune reactions.

在丙型肝炎病毒 (HCV) 感染中，众所周知，树突状细胞 (DC) 功能受损与肝病的发展以及抗病毒治疗（例如聚乙二醇干扰素组合）的耐药性密切相关-a和利巴韦林。我们在这个研究项目中证明，髓样 DC (MDC) 在响应 Toll 样受体 (TLR) 信号传导而产生 I 型 IFN 和 IL-12 方面功能受损，部分原因是 TRIF 和 TRIF 表达减少。 TRAF6 接头分子。此外，用HCV NS3/4A蛋白酶抑制剂治疗MDC恢复了MDC对CD4+T细胞的刺激能力。因此，我们证明MDC可以作为增强抗HCV免疫反应的治疗靶点。

项目成果

Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver.

• DOI: 10.1002/hep.23126
• 发表时间: 2009-10
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Hikita, Hayato;Takehara, Tetsuo;Shimizu, Satoshi;Kodama, Takahiro;Li, Wei;Miyagi, Takuya;Hosui, Atsushi;Ishida, Hisashi;Ohkawa, Kazuyoshi;Kanto, Tatsuya;Hiramatsu, Naoki;Yin, Xiao-Ming;Hennighausen, Lothar;Tatsumi, Tomohide;Hayashi, Norio
• 通讯作者: Hayashi, Norio

Replication-competent recombinant vesicular stomatitis virus encoding hepatitis C virus envelope proteins

• DOI: 10.1128/jvi.00608-07
• 发表时间: 2007-08-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Tani, Hideki;Komoda, Yasumasa;Matsuura, Yoshiharu
• 通讯作者: Matsuura, Yoshiharu

Anticancer Chemotherapy Inhibits MHC Class I-Related Chain A Ectodomain Shedding by Downregulating ADAM10 Expression in Hepatocellular Carcinoma

• DOI: 10.1158/0008-5472.can-09-0789
• 发表时间: 2009-10-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Kohga, Keisuke;Takehara, Tetsuo;Hayashi, Norio
• 通讯作者: Hayashi, Norio

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Virus associated innate immunity in liver.

病毒与肝脏的先天免疫相关。

• 发表时间: 2008
• 期刊: Frontiers in Bioscience 13
• 作者: Kurashige N.;Ohkawa;K;et al.;Kanto T.
• 通讯作者: Kanto T.