| Project/Area Number |
16K10171
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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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| Research Field |
Dermatology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
Kunimoto Kayo 和歌山県立医科大学, 医学部, 助教 (10438278)
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| Co-Investigator(Kenkyū-buntansha) |
金澤 伸雄 和歌山県立医科大学, 医学部, 准教授 (90343227)
稲葉 豊 和歌山県立医科大学, 医学部, 助教 (00647571)
邊見 弘明 和歌山県立医科大学, 先端医学研究所, 准教授 (20451924)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | PSMB9 / autoinflammatory / Nakajo-Nishimura / proteasome / PSMB8 / 中條ー西村症候群 / ノックインマウス / プロテアソーム / 中條-西村症候群 |
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| Outline of Final Research Achievements |
In a case with a novel heterozygous PSMB9 mutation, no apparent reduction of proteasome enzyme activity or ubiquitin accumulation was found, and it was thought that an unknown mechanism, not a simple dysfunction of the proteasome, contributes to the onset of autoinflammation. As a new patient with the same mutation have been found to show immunodeficiency with reduced peripheral blood CD8 and γδ T cells, defective NK cells and persistent polyoma virus infection, which were commonly observed in the mutation-knockin mice, the disease has been designated as proteasome-related autoinflammation and immunodeficiency disease (PRAID).
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| Academic Significance and Societal Importance of the Research Achievements |
我々の研究により、PSMB9の特異な変異によって、中條－西村症候群などのプロテアソーム関連自己炎症症候群（PRAAS）と異なり、免疫不全が前面に立つ、プロテアソーム関連自己炎症・免疫不全病（PRAID）を発症することが明らかとなった。新規PSMB9変異の病的意義の解明やプロテアソーム機能異常によって引き起こされる様々な臨床像の病態の解明を行うことにより、新たな治療標的となるシグナル分子の同定や、プロテアソームの新たな機能的意義や制御機構が明らかになることが期待される。
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