樹状細胞のウイルスパターン認識分子による細胞性免疫活性化機構

• 研究課題/領域番号: 19209015
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: ウイルス学
• 研究機関: 北海道大学
• 研究代表者: 瀬谷 司 北海道大学, 大学院・医学研究科, 教授 (10301805)
• 研究分担者: 松本 美佐子 北海道大学, 大学院・医学研究科, 准教授 (30332456) ; 赤澤 隆 大阪府立成人病センター, 研究所, 大阪府研究職 (80359299)
• 研究期間 (年度): 2007 – 2009
• 研究課題ステータス: 完了 (2009年度)
• 配分額: 48,620千円 (直接経費: 37,400千円、間接経費: 11,220千円); 2009年度: 15,340千円 (直接経費: 11,800千円、間接経費: 3,540千円); 2008年度: 15,340千円 (直接経費: 11,800千円、間接経費: 3,540千円); 2007年度: 17,940千円 (直接経費: 13,800千円、間接経費: 4,140千円)
• キーワード: 自然免疫 / TLR / TICAM-1 / IPS-1 / 樹状細胞 / NK細胞 / RNAパターン認識 / ワクチン / Toll-like receptor / TICAM-1経路 / Toll-like-receptor / Myd88経路 / polyI:C / TICAM-1(TRIF) / NK activation / Dendritic cell / RNA adjuvant / antitumor therapy / interferon (IFN) / adoptive transfer

研究概要

ウイルス感染の宿主2重鎖(ds)RNA応答を解析した。PolyI : C(dsRNA analog)刺激によって樹状細胞は細胞接着でNK細胞を活性化した。樹状細胞に発現誘導される膜分子から、NK活性化に必要な因子を同定し、INAMと名付けた。INAMはpolyI : C刺激の樹状細胞TICAM-1経路(TLR3)かIPS-1経路(MDA5)によって発現誘導され、in vivo polyI : C投与でも同じ結果が再現された。NK誘導によって移植がんの退縮も誘導された。

研究成果

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  • 雑誌名: J. Biol. Chem. (in press)
• [雑誌論文] Adjuvant engineering for cancer immunotherapy : development of a synthetic TLR2 ligand with increased cell adhesion (2010)
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  • 雑誌名: J. Exp. Med. (in press)
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  • 雑誌名: Cancer Sci. 101 ページ: 313-320
  • NAID: 10026587432
• [雑誌論文] Direct binding of TRAF2 and TRAF6 to TICAM-1/TRIF adaptor of the Toll-like receptor 3/4 pathway (2010)
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  • 雑誌名: Molec. Immunol. 47 ページ: 1283-1291
• [雑誌論文] Identification of INAM, a polyI : C-inducible membrane protein, that participates in dendritic cell-mediated natural killer cell activation. (2010)
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  • 査読あり
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  • 雑誌名: Eur.J.Immunol. (in press)
  • 査読あり
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  • 雑誌名: Cancer Science (in press)
  • NAID: 10026594411
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  • 著者名/発表者名: Seya, T., H.Shime, T.Ebihara, H.Oshiumi, M.Matsumoto.
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  • 雑誌名: Cancer Immunol. Immunother. 58 ページ: 1175-1184
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  • 雑誌名: Immunol. Rev. 227 ページ: 44-53
• [雑誌論文] Cytoplasmic oligomerized TICAM-1 recruits nuclear BS69 to enhance type I interferon induction (2009)
  • 著者名/発表者名: Takaki, H., H. Oshiumi, T. Kawanishi, M. Sasai, M. Matsumoto, T. Seya.
  • 雑誌名: Eur. J. Immunol. 39 ページ: 3469-3476
• [雑誌論文] Mitofusin 2, a mitochondrial fusion mediator, acts as a negative regulator for mitochondrial antiviral signaling (2009)
  • 著者名/発表者名: Yasukawa, K., H. Oshiumi, M. Takeda, Y. Yanagi, T. Seya, S. Kawabata, T. Koshiba.
  • 雑誌名: Science Signaling. 2(84)
• [雑誌論文] Innate Immunostimulatory lipopepitdes of Staphylococcus aureus as TLR2 ligands ; Prediction with mRNA expression, chemical synthesis and immunostimulatory activities (2009)
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  • 雑誌名: Chem Bio Chem. 10 ページ: 2311-2315
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  • 著者名/発表者名: Akao, Y., T. Ebihara, H. Masuda, Y. Saeki, K. Hazeki, O. Hazeki, M. Matsumoto, T. Seya.
  • 雑誌名: Cancer Sci. 100 ページ: 1494-1501
  • NAID: 10027193541
• [雑誌論文] Obstructing shedding of the immune stimulatory MHC class I chain-related gene B prevents tumor formation (2009)
  • 著者名/発表者名: Wu, J. D., C. L. Atteridge, X. J. Wang, T. Seya, S. R. Plymate
  • 雑誌名: Clin. Cancer Res. 15 ページ: 632-640
• [雑誌論文] Riplet/RNF135, a RING-finger protein, ubiquitinates RIG-I to promote interferon-β induction during the early phase of viral infection (2009)
  • 著者名/発表者名: Oshiumi, H., M. Matsumoto, S. Hatakeyama, T. Seya.
  • 雑誌名: J. Biol. Chem. 284 ページ: 807-817
• [雑誌論文] Oligomerized Toll-interleukin 1 receptor domain(TIR)-containing adaptor molecule-1 in the cytoplasm recruits nuclear adenovirus 5E1A-binding protein to enhance NF-kB activation and type I IFN induction. (2009)
  • 著者名/発表者名: Takaki, H., H.Oshiumi, M.Sasai, T.Kawanishi, M.Matsumoto, T.Seya.
  • 雑誌名: Eur.J.Immunol. 39 ページ: 3469-3476
  • 査読あり
• [雑誌論文] Dendritic cell/NK cell interaction in RNA virus infection. (2009)
  • 著者名/発表者名: Ebihara, T., M.Matsumoto, T.Seya.
  • 雑誌名: Current Immunol.Reviews 5 ページ: 200-207
• [雑誌論文] Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice. (2009)
  • 著者名/発表者名: Akao Y., T.Ebihara, H.Masuda, Y.Saeki, T.Akazawa, K.Hazeki, O.Hazeki, M.Matsumoto, T.Seya.
  • 雑誌名: Cancer Science 100 ページ: 1494-1501
  • NAID: 10027193541
  • 査読あり
• [雑誌論文] Riplet/RNF135, a RING-finger protein, ubiquitinates RIG-I to promote interferon-β induction during the early phase of viral infection. (2009)
  • 著者名/発表者名: Oshiumi, H., M.Matsumoto, S.Hatakeyama, T.Seya.
  • 雑誌名: J.Biol.Chem. 284 ページ: 807-817
  • 査読あり
• [雑誌論文] The extrinsic RNA-sensing pathway for adjuvant immunotherapy of cancer. (2009)
  • 著者名/発表者名: Seya, T., M.Matsumoto.
  • 雑誌名: Cancer Immunol.Immunother. 58 ページ: 1175-1184
• [雑誌論文] Functional evolution of the TICAM-1 pathway for extrinsic RNA sensing (2009)
  • 著者名/発表者名: Seya, T., M.Matsumoto, T.Ebihara, H.Oshiumi.
  • 雑誌名: Immunol.Reviews 227 ページ: 44-53
• [雑誌論文] Epstein-Barr virus(EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3. (2009)
  • 著者名/発表者名: Iwakiri, D., L.Zhou, M.Samanta, M.Matsumoto, T.Ebihara, T.Seya, S.Imai, M.Fujieda, K.Kawa, K.Takada.
  • 雑誌名: J.Exp.Med. 206 ページ: 2091-2099
  • NAID: 120001629790
  • 査読あり
• [雑誌論文] Toll受容体の機能 (2009)
  • 著者名/発表者名: 松本美佐子、瀬谷司
  • 雑誌名: 生化学 81 ページ: 156-164
• [雑誌論文] Mitofusin 2, a mitochondrial fusion mediator, acts as a negative regulator for mitochondrial antiviral signaling. (2009)
  • 著者名/発表者名: Yasukawa, K., H.Oshiumi, M.Takeda, Y.Yanagi, T.Seya, S.Kawabata, T.Koshiba
  • 雑誌名: Science Signaling 2(84)
  • 査読あり
• [雑誌論文] Pan-vertebrate Toll-like receptors during evolution. (review) (2009)
  • 著者名/発表者名: Oshiumi, H., Seya, T., et.al.
  • 雑誌名: Curr. Genomics 9 ページ: 488-493
  • 査読あり
• [雑誌論文] RiPlet / RNF 135, a RING-finger Protein, ubiquitinates RIG-I to Promote interferon-β induction during the early phase of viral infection (2009)
  • 著者名/発表者名: Oshiumi, H., Seva, T., et.al.
  • 雑誌名: J. Biol. Chem. 284 ページ: 807-817
  • 査読あり
• [雑誌論文] Obstructing shedding of the immune stimulatory MHC class I chain?related gene B prevents tumor formation (2009)
  • 著者名/発表者名: Wu, J. D., Seya, T., et.al.
  • 雑誌名: Clin. Cancer Res. 15 ページ: 632-640
  • 査読あり
• [雑誌論文] Functional evolution of the TICAM-1 (TRIF) pathway. for extrins is RNA sensing. (review) (2009)
  • 著者名/発表者名: Seya, T., et.al.
  • 雑誌名: Immunol. Rev. 227 ページ: 44-53
  • 査読あり
• [雑誌論文] Innate immune therapy with a BCG cell wall skeleton after radical surgery for non-small cell lung cancer : a case?control study (2009)
  • 著者名/発表者名: Kodama, K., Seya, T., et.al.
  • 雑誌名: Surgery Today. 39 ページ: 194-200
  • 査読あり
• [雑誌論文] The extrinsic RNA-sensing pathway for adjuvant immunotherapy Of cancer. (review) (2009)
  • 著者名/発表者名: Seya, T., et.al.
  • 雑誌名: Cancer Immunol. Immunother. (in press)
  • 査読あり
• [雑誌論文] NK cell licensing by dendritic cell in RNA virus infection. (review) (2009)
  • 著者名/発表者名: Ebihara, T., Seya, T., et.al.
  • 雑誌名: Curr. Immunol. Rev. (in press)
  • 査読あり
• [雑誌論文] Regulator of Complement Activation (RCA) gene cluster in Xenop us tropicalis (2009)
  • 著者名/発表者名: Oshiumi, H., Seva, T., et.al.
  • 雑誌名: Immunogenetics (in press)
  • 査読あり
• [雑誌論文] Asp-Glu-Ala-Asp / His (DEAD / H) BOX 3 (DDX3) helicase assembles in the IFN-βpromoter stimulator-1 (IPS-1)Pathway to enhance IFN-β induction. (2009)
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  • 雑誌名: PloS Pathol. (submitted)
  • 査読あり
• [雑誌論文] Specific recognition of diamilopimeric acid?containing peptidoglycan of Gram?negative bacteria by teleost Toll-like receptor 21 (2009)
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  • 査読あり
• [雑誌論文] Antitumor natural killer cell induction by orally administered Spirulina extract in mice (2009)
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  • 査読あり
• [雑誌論文] Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses (2008)
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• [雑誌論文] Hepatitis C virus (HCV)-infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and natural killer cells (2008)
  • 著者名/発表者名: Ebihara, T., M. Shingai, M. Matsumoto, T. Wakita, T. Seya.
  • 雑誌名: Hepatology. 48 ページ: 48-58
• [雑誌論文] Homo-oligomerization is essential for Toll/IL-1 receptor domain containing adaptor molecule-1-mediated NF-kappaB and interferon regulatory factor-3 activation (2008)
  • 著者名/発表者名: Funami K., M. Sasai, H. Oshiumi, T. Seya, M. Matsumoto
  • 雑誌名: J. Biol. Chem. 283 ページ: 18283-18291
• [雑誌論文] Modulation of Double-stranded RNA Recognition by the N-terminal Histidine-rich Region of the Human Toll-like Receptor 3 (2008)
  • 著者名/発表者名: Fukuda, K., T. Watanabe, T. Tokisue, T. Tsujita, S. Nishikawa, T. Hasegawa, T. Seya, M. Matsumoto.
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• [雑誌論文] The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-b production (2008)
  • 著者名/発表者名: Itoh, K., A. Watanabe, K. Funami, T. Seya, M. Matsumoto
  • 雑誌名: J. Immunol. 181 ページ: 5522-5529
• [雑誌論文] Tumor-secreted lactic acid promotes IL-23-IL-17 proinflammatory pathway (2008)
  • 著者名/発表者名: Shime, H., M. Yabu, T. Akazawa, K. Kodama, M. Matsumoto, T. Seya, N. Inoue.
  • 雑誌名: J. Immunol. 180 ページ: 7175-7183
• [雑誌論文] Soluble G protein of respiratory syncytial virus inhibts Toll-like receptor 3/4-mediated IFN-beta induction (2008)
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  • 著者名/発表者名: Bas, S., L. Neff, M. Vuillet, U. Spenato, T. Seya, M. Matsumoto, C. Gabay.
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  • 著者名/発表者名: Matsumoto, M., T. Seya.
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• [雑誌論文] Tumor-secreted lactic acid promotes IL-23-IL-17 proinflammatory pathway (2008)
  • 著者名/発表者名: Shime, H., Seya, T., et.al.
  • 雑誌名: J. Immunol 180 ページ: 7175-7183
  • 査読あり
• [雑誌論文] Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses (2008)
  • 著者名/発表者名: Matsuo, A., Seya, T., et.al.
  • 雑誌名: J. Immunol. 181 ページ: 3474-3485
  • 査読あり
• [雑誌論文] Increased expression of Toll-like receptor3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers (2008)
  • 著者名/発表者名: Nakamura, M., Seya, T., et.al.
  • 雑誌名: Hepatology International. 2 ページ: 222-230
  • 査読あり
• [雑誌論文] Homo-oligomerization is essential for Toll / IL-1 receptor domain containing adaptor molecule-1-mediated NF-kappaB and interferon regulatory factor-3 activation. (2008)
  • 著者名/発表者名: Funami K., Seya, T., et.al.
  • 雑誌名: J. Biol. Chem. 283 ページ: 18283-18291
  • 査読あり
• [雑誌論文] Modulation of Double-stranded RNA Recognition by the N-terminal Histidine-rich Region of the Human Toll-like Receptor 3. (2008)
  • 著者名/発表者名: Fukuda, K., Seya, T., et.al.
  • 雑誌名: J. Biol. Chem. 283 ページ: 22787-22794
  • 査読あり
• [雑誌論文] Hepatitis C virus (HCV)-infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and NK cells (2008)
  • 著者名/発表者名: Ebihara, T., Seya, T., et.al.
  • 雑誌名: Hepatology. 48 ページ: 48-58
  • 査読あり
• [雑誌論文] Soluble G protein of respiratory syncytial virus inhibts Toll-like receptor 3/4-mediated IFN-beta induction. (2008)
  • 著者名/発表者名: Shingai, M., Seya, T., et.al.
  • 雑誌名: Int. Immunol. 20 ページ: 1169-1180
  • 査読あり
• [雑誌論文] Selective synergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cells. (2008)
  • 著者名/発表者名: Hirata, N., Seya, T., et.al.
  • 雑誌名: Mol. Immunol. 45 ページ: 2734-2742
  • 査読あり
• [雑誌論文] The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-β production (2008)
  • 著者名/発表者名: Itoh, K., Seva, T., et.al.
  • 雑誌名: J.Immunol. 181 ページ: 5522-5529
  • 査読あり
• [雑誌論文] Tumor-secreted lactic acid promotes IL-23-IL-7 proinflammatory pathway (2008)
  • 著者名/発表者名: Shime, H., et. al.
  • 雑誌名: J. Immunol. 180 ページ: 7175-7183
  • 査読あり
• [雑誌論文] Hepatitis C virus (HCV)-infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and NK cells (2008)
  • 著者名/発表者名: Ebihara, T., et. al.
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  • 査読あり
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