| Project/Area Number |
15K06811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Research Collaborator |
Negishi Yasuyuki 日本医科大学, 微生物学・免疫学分野, 講師
Maruyama Motoyo 日本医科大学, 実験動物管理施設, 助教
Shimizu Masumi 日本医科大学, 徴生物学・免疫学分野, 技術員
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | AIDS / HIV-1 / ヒト化マウス / ウイルス感染 / ウイルス / 自然免疫応答 / 感染 / 造血幹細胞 / 自然免疫 / 間葉系・間質系幹細胞 / 造血系幹細胞 |
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| Outline of Final Research Achievements |
In this study, we established a humanized mouse model where innate immune cells are efficiently reconstituted in order to unveil the viral dynamics and the locally induced innate immunity at very early time points after human immunodeficiency virus type 1 (HIV-1) inoculation.
We observed the successful reconstitution of human innate immune cells including Langerhans cells in the skin epithelia of the newly established humanized mice by injection of cocultured human haematopoitic and messenchymal stem cells. After intrarectal inoculation, the challenge virus resided at the anal side of the rectum, and some virus particles were found inside rectal villi as early as three hours after inoculation, suggesting much earlier incorporation of virus particles into the rectum tissue than previously thought. We are currently analyzing systematically the immune cells surrounding the infected cells to clarify the innate immune response to HIV-1 infection at the vey early phase of infection.
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| Academic Significance and Societal Importance of the Research Achievements |
AIDSは世界で毎年数千万人もの新規患者が出る新興感染症で、日本では先進国で唯一患者数が増え続けているが、根本的な治療方法はまだ開発されていない。本研究では、粘膜および皮膚内の自然免疫のヒト化を強化したマウスを確立し、AIDS病態における異常な免疫活性化とそれに続く免疫不全を誘発する原因を自然免疫の観点から探求した。少なくとも経直腸感染では感染後6時間以内にCD4陽性細胞の近傍にウイルスが認められ、ウイルスの体内への侵入は従来考えられていたよりも早いことが明らかとなった。本研究が今後、HIV-1感染がAIDSという病態を引き起こすメカニズムを解明し、早期治療方法の開発に繋がると期待している。
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