| Project/Area Number |
17K15665
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 形質細胞様樹状細胞 / インターフェロン / I型IFN |
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| Outline of Final Research Achievements |
Plasmacytoid dendritic cell (pDC) is a unique cell population that produces large amounts of type I interferon (IFN-a/IFN-b) via TLR7/9-mediated recognition of a single-stranded RNA or CpG DNA. We have shown that an Ets family transcription factor SpiB can transactivate IFN-a promoter in synergy with IFN regulatory factor-7 (IRF7), and is required for type I IFN production in pDC. However, how pDC negatively regulates type I IFN induction remains unknown.
In this study, we show that transcription factor HS01 can suppress the induction of IFN-a and IFN-b by interacting with SpiB/IRF7 complex. HS01 mRNA expression decreased in TLR7/9-stimulated pDC and HS01 protein was degraded by the ubiquitin-proteasome system in the early phase. Our findings show a role for HS01 as a negative regulator of type I IFN induction in pDC.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりpDCによるI型IFN産生メカニズムの理解が深まれば、pDCを標的としたSLEなどの自己免疫疾患に対する治療薬開発の分子基盤を提供することになり、臨床的応用にも繋げることが可能になる。さらに、HS01を標的として宿主内に侵入・潜伏している病原体の感染戦略の理解や問題提起を促すことにも繋がり、専門分野だけでなく分野外にも波及効果をもたらすことが予想され、その社会的意義は極めて大きいと考えられる。
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