| Project/Area Number |
15K09550
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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 |
Collagenous pathology/Allergology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 膠原病 / インターフェロン / 核酸 / SLE / 診断 / 核酸受容体 / 内因性膜小胞 / I型IFN / 膜小胞 / 細胞外核酸 / cGAS–STING / type I IFN / アポトーシス / 細胞外膜小胞 / STING / cGAS / 遺伝子改変技術 / 炎症 / 自己免疫疾患 / 自然免疫受容体 / レポーター細胞 / エクソソーム |
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| Outline of Final Research Achievements |
Systemic lupus erythematosus (SLE) is an autoimmune disease that predominates in young women with various organ disorders, and it is pointed out that one of the etiologies is type I interferon (IFN-I) associated with the failure of immune tolerance to its own nuclear components. It has been known that measuring IFN-I in actual SLE patients is difficult due to the low sensitivity of the ELISA method, but we revealed that by using reporter cells, it become possible to evaluate IFN-I activity in serum. Then, we clarified that 1) IFN-I activity and IFN-I-inducing activity is high in SLE serum, 2) there are apoptotic cell-derived membrane vesicles (AdMVs) which contain double-stranded DNA in SLE serum promoted additional production of IFN-I, and that 3) IFN-I production by AdMVs was mediated via the cGAS-STING pathway. These findings are considered to provide the effective and safe medical treatment for SLE.
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| Academic Significance and Societal Importance of the Research Achievements |
SLEに対してインターフェロン受容体を標的とした治療薬開発が進められていますが、すべての患者さんにが有効なわけではありません。レポーター細胞によるモニタリングは、インターフェロン治療が効く症例の層別化に有用で、治療効果のモニタリングにも応用可能であると思われます。また、SLE患者血清における膜小胞を介したインターフェロン産生経路の存在は、今後のより効果的な治療薬の開発に、重要なヒントとなる成果だと思われます。
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