Spatiotemporal regulation of nucleic acid uptake and signaling
Project/Area Number |
23590558
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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 |
Research Field |
Immunology
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Research Institution | Hokkaido University |
Principal Investigator |
MATSUMOTO Misako 北海道大学, 医学(系)研究科(研究院), 特任准教授 (30332456)
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Co-Investigator(Renkei-kenkyūsha) |
SEYA Tsukasa 北海道大学, 大学院医学研究科, 教授 (10301805)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | 自然免疫 / Toll-like receptor / エンドソーム / 樹状細胞 / RNA認識 / ウイルス感染 / 炎症応答 / マクロファージ / RNA / エンドサイトーシス / インターフェロン / 細胞死 / アジュバント / 核酸 / シグナル伝達 / サイトカイン |
Research Abstract |
Endosomal Toll-like receptor (TLR) 3 serves as a sensor of viral infection and sterile tissue necrosis and activates innate and adaptive immunity. Although TLR3 recognizes double-stranded (ds) RNA, little is known about structural features of virus- or host-derived RNAs that activate TLR3 in infection/inflammatory states. In this study, we demonstrate that single-stranded RNAs harboring stable incomplete stem structures are potent TLR3 agonists. Like poly(I:C), a synthetic dsRNA, these structured RNAs were internalized into cells via raftlin-mediated endocytosis and activated TLR3. Based on the ligand recognition mode of TLR3 and uptake mechanism of extracellular nucleic acids, we have generated novel TLR3 ligand that activates endosomal TLR3 but not cytoplasmic RNA sensors.
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Report
(4 results)
Research Products
(102 results)
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[Journal Article] Structures and interface mapping of the TIR-domain-containing adaptor molecules involved in interferon signaling2013
Author(s)
Enokizono, Y., H. Kumeta, K. Funami, M. Horiuchi, J. Sarmiento, K. Yamashita, D. Standley, M. Matsumoto, T. Seya, and F. Inagaki.
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Journal Title
Proc. Natl. Acad. Sci. U. S. A.
Volume: 110(49)
Pages: 19908-19913
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[Journal Article] Cleaved/associated TLR3 represents the primary form of the signaling receptor2013
Author(s)
Toscano F., Y. Estornes, F. Virard, A. Garcia-Cattaneo, A. Pierrot, B. Vanbervliet, M. Bonnin, M. J. Ciancanelli, S-Y. Zhang, K. Funami, T. Seya, M. Matsumoto, J-J. Pin, J-L. Casanova, T. Renno, and S. Lebecque.
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Journal Title
J Immunol
Volume: 190(2)
Pages: 764-773
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[Journal Article] Cleaved/associated TLR3 represents the primary form of the signaling receptor.2013
Author(s)
Toscano F, Estornes Y, Virard F, Garcia-Cattaneo A, Pierrot A, Vanbervliet B, Bonnin M, Ciancanelli MJ, Zhang SY, Funami K, Seya T,Matsumoto M, Pin JJ, Casanova JL, Renno T, Lebecque S.
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Journal Title
J Immunol.
Volume: 190(2)
Issue: 2
Pages: 764-773
DOI
Related Report
Peer Reviewed
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[Journal Article] Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes2012
Author(s)
Naito, A. T., T. Sumida, S. Nomura, M-L Liu, T. Higo, K. A. Nakagawa, Okada, T. Sakai, A. A. Hashimoto, Y. Hara, I. Shimizu, W. Zhu, H. Toko, A. Katada, H. Akazawa, T. Oka, J-K. Lee, T. Minamino, T. Nagai, K. Walsh, A. Kikuchi, M. Matsumoto, M. Botto, I. Shiojima, and I. Komuro.
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Journal Title
Cell
Volume: 149(6)
Pages: 1298-1313
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[Journal Article] Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes2012
Author(s)
Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, Okada K, Sakai T, Hashimoto A, Hara Y, Shimizu I, Zhu W, Toko H, Katada A, Akazawa H, Oka T, Lee JK, Minamino T, Nagai T, Walsh K, Kikuchi A, Matsumoto M, Botto M, Shiojima I, Komuro I
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Journal Title
Cell
Volume: 149
Issue: 6
Pages: 1298-1313
DOI
Related Report
Peer Reviewed
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[Journal Article] Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR22011
Author(s)
Sawahata, R., Shime, H., Yamazaki, S., Inoue, N., Akazawa, T., Fujimoto, Y., Fukase, K., Matsumoto, M. and Seya, T.
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Journal Title
Microbes and Infection
Volume: 13
Issue: 4
Pages: 350-358
DOI
NAID
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Peer Reviewed
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[Book] Jesus Giraldo, editors : Oligomerization in Health and Disease, Vol 117, PMBTS, UK, Toll-IL-1-receptor-containing adaptor molecule-1 (TICAM-1), a signaling adaptor linking innate immunity to adaptive immunity2013
Author(s)
Matsumoto, M., K. Funami, H. Oshiumi, and T. Seya.
Publisher
Academic Press
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