| Project/Area Number |
18K08343
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 機能的遺伝子多型 / 造血幹細胞移植 / 遺伝子多型 / マイクロRNA / 免疫制御 / 造血細胞移植 |
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| Outline of Final Research Achievements |
In this study, the functional roles of immunomodulatory gene polymorphisms in the 5’-untranslated region (NLRP3, ADMTS13, UNC93B1, HO-1), which the principal investigator has previously shown affect survival outcomes after allogeneic hematopoietic stem cell transplantation, were demonstrated. In particular, it was found that the G and C alleles in the NLRP3 rs10754558 (G > C) have high inducibility of NLRP3 / IL-1b and low inducibility of NLRP3 / IL-1b, respectively. In addition, allogeneic hematopoietic stem cell transplant recipients with the NLRP3 rs10754558 G allele were suggested to have increased mortality from transplant-related complications due to their high IL-1b inducibility. These results will also lead to the development of new targeted therapies for solid cancers, autoimmune diseases, and severe infectious diseases in which immunomodulatory gene polymorphisms are involved in their onset and progression of diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
同種造血幹細胞移植は白血病など血液難病の根治を期待して行われる。しかし、重症感染症や拒絶反応、再発のため、長期生存率は50%にとどまる。本研究において、下流非翻訳領域の機能性免疫調整遺伝子多型を制御することにより、同種造血幹細胞の成功率が飛躍的に高まる可能性が示された。さらに今回の研究成果は、同種造血幹細胞移植にとどまらず、疾患の発症や進展に免疫調整遺伝子多型が関与する固形がんや自己免疫疾患、重症感染症に対する新規標的治療法開発への波及効果も期待される。
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