| Project/Area Number |
18K15131
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | B型肝炎ウイルス / 細胞外小胞 / ハイドロダイナミックインジェクション / PD-L1 / 腸管免疫 / HBV / 肝臓 / 腸管 / 腸内細菌叢 / 骨髄 |
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| Outline of Final Research Achievements |
In this study, we used a mouse model of HBV infection to elucidate the effects of extracellular vesicles (EVs) derived from HBV-infected cells on HBV-related pathologies and their role in intestinal immunity. The results showed that EVs secreted from cells with HBV infection strongly suppressed the immune response, which inhibited the eradication of HBV-replicating cells in the HBV mouse model of infection. It was suggested that up-regulation of PD-L1 expression in dendritic cells in liver-draining lymph nodes may be important for the suppression of this eradication. Furthermore, the addition of infected cell-derived EVs to the culture supernatant of bone marrow cells increased the proportion of CD11c+ CD11b+ CD103+ cells, an immunomodulatory DC population in the gut. These results suggest that bone marrow cells that take up EVs derived from HBV-infected cells may affect intestinal immunity.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、HBV感染細胞から放出される細胞外小胞(EVs)の機能を解析した研究はなされてきたが、全てIn vitroでの研究であった。本研究は、HBV感染マウスモデルを使って初めてIn vivoでHBV感染細胞由来EVsの機能を明らかにしたものである。この機能は、HBV感染細胞由来EVsは免疫応答を強く抑制し、HBV複製細胞の排除を抑制するものである。さらに、HBV感染細胞由来EVsは腸管免疫にも影響与えている可能性を示唆する結果も得られた。これらの結果は、B型肝炎関連病態の理解を深めるとともに、新規治療の開発への足がかりとなることも期待できる。
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