Regulation of T-cell activation and cellular immune response by intracellular activation of complement C3 in fish
Project/Area Number |
19H03050
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 40040:Aquatic life science-related
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Research Institution | Kyushu University |
Principal Investigator |
NAKAO Miki 九州大学, 農学研究院, 教授 (50212080)
|
Co-Investigator(Kenkyū-buntansha) |
杣本 智軌 九州大学, 農学研究院, 准教授 (40403993)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2021: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2020: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
|
Keywords | 補体 / C3 / 細胞内活性化 / コイ / 白血球 / 魚類 / カテプシンL / エンドサイトーシス / プロテアーゼ / 遺伝子ノックダウン / 上皮細胞 / 断片化 / アイソタイプ / T細胞 |
Outline of Research at the Start |
本研究は、コイおよびギンブナをモデルとして用い、魚類血球の細胞内におけるC3の活性化機構と、この活性化による免疫応答の制御機構を解明し、補体を介した細胞性免疫応答の強化と制御法を見出すことを目的とする。具体的には、細胞内C3活性化が起こる細胞種の特定および各細胞種においてC3の活性化を担うプロテアーゼの同定を進める。さらに細胞内C3活性化が各細胞種によるサイトカイン産生プロファイルに及ぼす影響を精査する。
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Outline of Final Research Achievements |
Recently, physiological effects of intracellular complement activation in mammals have attracted much attention, but its phylogenetic development has not been investigated at all. To elucidate the phylogeny and physiological function of intracellular complement activation, this study aimed to detect activated fragments of the complement component C3 in carp leukocyte cells and to identify proteases involved in intracellular C3 fragmentation. The results suggested that C3 is present in carp leukocytes and undergoes limited hydrolysis, which is different from complement activation, on a permanent basis, and that little remains in the unactivated form; that this limited hydrolysis is caused by proteases other than cathepsin L, unlike that reported for human cells; and that C3 may be taken up and fragmented from the extracellular C3 from outside the cell and fragmentation.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、プロテアーゼの特定には至らなかったものの、コイPBL内C3の存在と断片化が示された。本研究成果は、学術的には細胞内補体系の系統発生と生理機能の理解を深める重要な知見であるだけでなく、細胞内補体活性化を指標とした、魚類の生体防御能レベルのモニタリング法の開発などの応用につながると期待される。
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Report
(4 results)
Research Products
(21 results)