| Project/Area Number |
18K15189
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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 49070:Immunology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Hiroki Tanaka 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (50747920)
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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 | mRNA分解酵素 / Regnase-1 / mRNA安定性 / 炎症 / 炎症反応 / IL-17 / リン酸化 / 細胞内局在 / IL17 / 小胞体 / 炎症反応制御 / RNA安定性 / TH17細胞 / 自己免疫疾患 |
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| Outline of Final Research Achievements |
Regnase-1is an endoribonuclease that regulates immune response through its enzymatic activity. Regnase-1 is induced upon stimulation with TLR ligands or proinflammatory cytokines, and degrades inflammation-associated mRNAs, thereby forming a negative feedback circuit to diminish excess inflammatory response. In this grant, I focused on inactivation mechanism of Regnase-1 mediated by proinflammatory cytokine Interleukin-17 and tried to elucidate the molecular mechanism of this inactivation. And I found that Regnase-1 phosphorylation resulted in a change in subcellular localization of Regnase-1 proteins from the endoplasmic reticulum to the cytosols. This translocation leads to attenuation of the RNase activity of Regnase-1. These results suggest that Regnase-1 phosphorylation is important for fine-tuning of the expression levels of IL-17-associated inflammatory genes and controlling IL-17-mediated inflammatory diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、Rengnase-1遺伝子がインターロイキン１７の関与する慢性炎症疾患の症状を制御する重要な因子であり、インターロイキン１７による細胞刺激によって誘発されるRegnase-1蛋白質のリン酸化が炎症状態の維持における鍵となる現象であることを明らかにした。またRegnase-1のリン酸化の阻害は、これらの疾患を治療する有力なストラテジーとなり得ることを示した。
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