Inflammatory response regulation by immune system specific autophagy regulator Rufy4
Project/Area Number |
18K06937
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48040:Medical biochemistry-related
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Research Institution | Osaka City University |
Principal Investigator |
TERAWAKI Seigo 大阪市立大学, 大学院医学研究科, 助教 (60437217)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | オートファジー / メンブレントラフィッキング / NETosis / 炎症性疾患 / 分子免疫制御 / 炎症応答 / 免疫応答制御 / 炎症 / ユビキチン / シグナル伝達 / メンブレントラフィック |
Outline of Final Research Achievements |
To elucidate the pathophysiological function of immune system-specific autophagy regulator Rufy4 which is constantly expressed in neutrophil, we investigated the involvement of Rufy4 in NETosis progression. Non-inflammatory neutrophils are isolated from wild type, or rufy4-deficient mice peritoneal wash by density-gradient centrifugation. Although NETosis was induced both in wild type and rufy4 deficient neutrophils, NETs expelled from rufy4 KO neutrophil was drastically reduced as compared to wild type. This result suggested that Rufy4 has a critical role in NETosis progression, but not in initiation.
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Academic Significance and Societal Importance of the Research Achievements |
好中球は感染初期における生体防御を担っており、感染の負荷が高い場合にはNETosisとよばれる細胞死を誘導し、分泌顆粒内の消化酵素とともに自らのクロマチンDNAを放出して細菌を物理的に捕捉殺菌していることが知られているが、その分子メカニズムはまだ不明な点が多い。本研究において免疫系特異的オートファジー制御因子であるRufy4がNETosisの進行に重要な機能を持っていることが示唆された。NETosisは自己免疫疾患や血管炎、さらにはCOPDやCOVID-19など炎症性肺疾患への関与も指摘されており、本研究はこれら難治性炎症疾患の病態解明や治療法開発に繋がることが期待される。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Molecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses.2020
Author(s)
Oikawa D, Sato Y, Ohtake F, Komakura K, Hanada K, Sugawara K, Terawaki S, Mizukami Y, Phuong HT, Iio K, Obika S, Fukushi M, Irie T, Tsuruta D, Sakamoto S, Tanaka K, Saeki Y, Fukai S, Tokunaga F.
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Journal Title
Commun. Biol.
Volume: 3
Issue: 1
Pages: 163-163
DOI
Related Report
Peer Reviewed / Open Access
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