| Project/Area Number |
18K17418
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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 58040:Forensics medicine-related
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | アセトアミノフェン / 肝障害 / 法医中毒学 / 法医学 / 樹状細胞 |
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| Outline of Final Research Achievements |
We focused XCR1-expressing dendritic cells which involved the amplification and suppression of inflammatory and researched the role of them in APAP induced liver injury by using mice models (Wild type and knockout of XCR1). After APAP challenge, liver injury was aggravated in Xcr1-/- mice compared with wild type. In the wild type, after APAP challenge, the expression of XCL1 and XCR1 in the liver decreased after 10 hours of administration and then increased and returned to the original level at 30 hours. This is thought to be due to the replenishment of XCL1-positive cells necrotic due to APAP liver injury. The same trend of XCL1 expression was observed in Xcr1-/-mice after APAP challenge. Replenished XCL1-expressing cells recruit XCR1-expressing cells. Namely, it was suggested that the infiltration of XCR1-positive cells into the liver is involved in the suppression of inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
近年，臨床医学領域において，免疫機能における樹状細胞の動態と種々の疾患の病態との関わりについて研究が盛んになされ，炎症性疾患，癌，疼痛などの疾患の病態生理において樹状細胞が密接に関与していることが明らかとなっている．本研究を通じて，XCR1陽性樹状細胞がAPAP肝障害における「鍵となる細胞種」であることが明らかとなれば，従来の化学分析結果と樹状細胞の動態を有機的に組み合わせることによって，これまで以上に客観的かつ正確な死因の判断が可能となることが予想される．さらに，本研究は免疫学，薬理学，救急医学と密接に関連する学際的研究であり，法医学を発信源とした医科学の発展に寄与する将来性のある研究である
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