2022 Fiscal Year Final Research Report
Analysis of immune regulatory mechanisms mediated by mRNA metabolism
| Project/Area Number |
18H05278
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Review Section |
Broad Section H
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
植畑 拓也 京都大学, 医学研究科, 助教 (50785970)
三野 享史 京都大学, 医学研究科, 助教 (60646149)
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| Project Period (FY) |
2018-06-11 – 2023-03-31
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| Keywords | 炎症性疾患 / mRNA分解 / 核酸医薬 / 免疫細胞分化 / mRNA修飾 |
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| Outline of Final Research Achievements |
We showed that the expression of Regnase-1, a protein involved in the degradation of mRNA such as cytokines, in immune cells is associated with human pulmonary hypertension. We also discovered that mice lacking Regnase-1 in myeloid cell lineage cells naturally developed pulmonary hypertension. Furthermore, we succeeded in the development of nucleic acid therapeutics that enhance Regnase-1 expression and suppress inflammation was achieved by targeting the self-regulatory mechanism of Regnase-1. In addition, through analysis of the relationship between mRNA modification and blood cell differentiation, we found that mice lacking the RNA m6A methylation enzyme METTL16 exhibit severe anemia through DNA repair impairment. This finding demonstrates the important role of m6A modification mediated by METTL16 in hematopoietic cell differentiation.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、免疫細胞におけるmRNA分解や修飾と知った制御システムが、さまざまなヒト免疫・炎症性疾患に関わる事が明らかとなった。さらに、免疫制御における分子機構が解明され、それを利用した核酸医薬による免疫制御法の開発に発展した。これらは、学術的にも新規のものであり、これまでに明らかとなっている転写やシグナル伝達制御とは異なるユニークな機構である。自己免疫疾患や炎症性疾患といった疾患の治療法開発や、逆に、免疫応答を亢進させることで、癌免疫療法の進展や新たなワクチンアジュバント開発に寄与する事が期待される。
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