Pattern-recognition receptors in dendritic cells evoke cellular immunity in response to viral RNA patterns

2009 Fiscal Year Final Research Report

• Project/Area Number: 19209015
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: SEYA Tsukasa Hokkaido University, 大学院・医学研究科, 教授 (10301805)
• Co-Investigator(Kenkyū-buntansha): MATSUMOTO Misako 北海道大学, 大学院・医学研究科, 准教授 (30332456) ; AKAZAWA Takashi 大阪府立成人病センター, 研究所, 大阪府研究職 (80359299)
• Project Period (FY): 2007 – 2009
• Keywords: 自然免疫 / TLR / TICAM-1 / IPS-1 / 樹状細胞 / NK細胞 / RNAパターン認識

Research Abstract

How host cells respond to viral dsRNA is analyzed in this study. Dendritic cells (DC) stimulated with polyI : C (an dsRNA analog) render the DC competent for NK activation. Since cell-cell contact was essential for this NK activation, the molecule expressed on DC to drive NK activation was identified from genes up-regulated by polyI : C stimulation. Ultimately, we identified a membrane protein responsible for NK induction and named it INAM. INAM is a tetraspanin-like molecule inducing NK tumoricidal activity and in vivo tumor regression.

Research Products

• [Journal Article] Molecular mechanism for activation of Toll/IL-1 receptor domain-containing adaptor molecule-1 (TICAM-1) (2010)
  • Author(s): Tatematsu, M., A. Ishii, M. Horiuchi, H. Oshiumi, F. Inagaki, T. Seva, M. Matsumoto.
  • Journal Title: J. Biol. Chem. (in press)
• [Journal Article] Adjuvant engineering for cancer immunotherapy : development of a synthetic TLR2 ligand with increased cell adhesion (2010)
  • Author(s): Akazawa, T., N. Inoue, H. Shime, K. Sugiura, K. Kodama, M. Matsumoto, T. Seya.
  • Journal Title: Cancer Sci (in press)
• [Journal Article] DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-beta inducing potential (2010)
  • Author(s): Oshiumi, H., K. Sakai, M. Matsumoto, T. Seya.
  • Journal Title: Eur. J Immunol (in press)
• [Journal Article] Identification of INAM, a polyI : C-inducible membrane protein, that participates in dendritic cell-mediated natural killer cell activation (2010)
  • Author(s): Ebihara, T., M. Azuma, H. Oshiumi, M. Matsumoto, T. Seva.
  • Journal Title: J. Exp. Med. (in press)
• [Journal Article] Innate immunity and vaccine (2010)
  • Author(s): Seva, T.
  • Journal Title: Vaccine (in press)
• [Journal Article] Pattern-recognition receptors of innate immunity and their application to tumor immunotherapy (2010)
  • Author(s): Seva, T., H. Shime, T. Ebihara, H. Oshiumi, M. Matsumoto.
  • Journal Title: Cancer Sci. 101 Pages: 313-320
• [Journal Article] Direct binding of TRAF2 and TRAF6 to TICAM-1/TRIF adaptor of the Toll-like receptor 3/4 pathway (2010)
  • Author(s): Sasai, M., H. Oshiumi, K. Funami, M. Matsumoto, T. Seya.
  • Journal Title: Molec. Immunol. 47 Pages: 1283-1291
• [Journal Article] Innate immune therapy with a BCG cell wall skeleton for lung cancer : a case presentation and a case control study (2009)
  • Author(s): Kodama, K., M. Higashiyama, K. Takami, K. Oda, J. Okami, J. Maeda, T. Akazawa, M. Matsumoto, T. Seya, M. Wada, A. Hayashi, K. Toyoshima.
  • Journal Title: Surgery Today. 39 Pages: 194-200
• [Journal Article] Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from Toll-like receptor 3 (2009)
  • Author(s): Iwakiri. D., L. Zhou, M. Samanta, M. Matsumoto, T. Ebihara, T. Seya, S. Imai, M. Fujieda, K. Kawa, K. Takada.
  • Journal Title: J. Exp. Med. 206 Pages: 2091-2099
• [Journal Article] The extrinsic RNA-sensing pathway for adjuvant immunotherapy for cancer (2009)
  • Author(s): Seya. T., M. Matsumoto.
  • Journal Title: Cancer Immunol. Immunother. 58 Pages: 1175-1184
• [Journal Article] Functional evolution of the TICAM-1 (TRIF) pathway for extrinsic RNA sensing (2009)
  • Author(s): Seya. T., M. Matsumoto, T. Ebihara, H. Oshiumi.
  • Journal Title: Immunol. Rev. 227 Pages: 44-53
• [Journal Article] Cytoplasmic oligomerized TICAM-1 recruits nuclear BS69 to enhance type I interferon induction (2009)
  • Author(s): Takaki, H., H. Oshiumi, T. Kawanishi, M. Sasai, M. Matsumoto, T. Seya.
  • Journal Title: Eur. J. Immunol. 39 Pages: 3469-3476
• [Journal Article] Mitofusin 2, a mitochondrial fusion mediator, acts as a negative regulator for mitochondrial antiviral signaling (2009)
  • Author(s): Yasukawa, K., H. Oshiumi, M. Takeda, Y. Yanagi, T. Seya, S. Kawabata, T. Koshiba.
  • Journal Title: Science Signaling. 2(84) Pages: ra47
• [Journal Article] Innate Immunostimulatory lipopepitdes of Staphylococcus aureus as TLR2 ligands ; Prediction with mRNA expression, chemical synthesis and immunostimulatory activities (2009)
  • Author(s): Fujimoto, Y., M. Hashimoto, M. Furuyashiki, M. Katsumoto, T. Seya, Y. Suda, K. Fukase.
  • Journal Title: Chem Bio Chem. 10 Pages: 2311-2315
• [Journal Article] Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice (2009)
  • Author(s): Akao, Y., T. Ebihara, H. Masuda, Y. Saeki, K. Hazeki, O. Hazeki, M. Matsumoto, T. Seya.
  • Journal Title: Cancer Sci. 100 Pages: 1494-1501
• [Journal Article] Obstructing shedding of the immune stimulatory MHC class I chain-related gene B prevents tumor formation (2009)
  • Author(s): Wu, J. D., C. L. Atteridge, X. J. Wang, T. Seya, S. R. Plymate
  • Journal Title: Clin. Cancer Res. 15 Pages: 632-640
• [Journal Article] Riplet/RNF135, a RING-finger protein, ubiquitinates RIG-I to promote interferon-β induction during the early phase of viral infection (2009)
  • Author(s): Oshiumi, H., M. Matsumoto, S. Hatakeyama, T. Seya.
  • Journal Title: J. Biol. Chem. 284 Pages: 807-817
• [Journal Article] Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses (2008)
  • Author(s): Matsuo, A., H. Oshiumi, T. Tsujita, H. Mitani, H. Kasai, M. Yoshimizu, M. Matsumoto, T. Seya.
  • Journal Title: J. Immunol. 181 Pages: 3474-3485
• [Journal Article] Hepatitis C virus (HCV)-infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and natural killer cells (2008)
  • Author(s): Ebihara, T., M. Shingai, M. Matsumoto, T. Wakita, T. Seya.
  • Journal Title: Hepatology. 48 Pages: 48-58
• [Journal Article] Homo-oligomerization is essential for Toll/IL-1 receptor domain containing adaptor molecule-1-mediated NF-kappaB and interferon regulatory factor-3 activation (2008)
  • Author(s): Funami K., M. Sasai, H. Oshiumi, T. Seya, M. Matsumoto
  • Journal Title: J. Biol. Chem. 283 Pages: 18283-18291
• [Journal Article] Modulation of Double-stranded RNA Recognition by the N-terminal Histidine-rich Region of the Human Toll-like Receptor 3 (2008)
  • Author(s): Fukuda, K., T. Watanabe, T. Tokisue, T. Tsujita, S. Nishikawa, T. Hasegawa, T. Seya, M. Matsumoto.
  • Journal Title: J. Biol. Chem. 283 Pages: 22787-22794
• [Journal Article] The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-b production (2008)
  • Author(s): Itoh, K., A. Watanabe, K. Funami, T. Seya, M. Matsumoto
  • Journal Title: J. Immunol. 181 Pages: 5522-5529
• [Journal Article] Tumor-secreted lactic acid promotes IL-23-IL-17 proinflammatory pathway (2008)
  • Author(s): Shime, H., M. Yabu, T. Akazawa, K. Kodama, M. Matsumoto, T. Seya, N. Inoue.
  • Journal Title: J. Immunol. 180 Pages: 7175-7183
• [Journal Article] Soluble G protein of respiratory syncytial virus inhibts Toll-like receptor 3/4-mediated IFN-beta induction (2008)
  • Author(s): Shingai, M., M. Azuma, T. Ebihara, M. Sasai, K. Funami, M. Ayata, H. Ogura, H. Tsutsumi, M. Matsumoto, T. Seya
  • Journal Title: Int. Immunol. 20 Pages: 1169-1180
• [Journal Article] The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14 (2008)
  • Author(s): Bas, S., L. Neff, M. Vuillet, U. Spenato, T. Seya, M. Matsumoto, C. Gabay.
  • Journal Title: J. Immunol. 180 Pages: 1158-1168
• [Journal Article] TLR3 : interferon induction by double-stranded RNA including poly (I:C). (2008)
  • Author(s): Matsumoto, M., T. Seya.
  • Journal Title: Adv. Drug Deliv. Rev. 60 Pages: 805-812
• [Journal Article] NKG2D ligands are induced on human dendritic cells by TLR ligand stimulation and RNA virus infection (2007)
  • Author(s): Ebihara, T., H. Masuda, T. Akazawa, M. Shingai, H. Kikuta, T. Ariga, M. Matsumoto, T. Seya.
  • Journal Title: Int. Immunol. 19 Pages: 1145-1155
• [Journal Article] Spatiotemporal mobilization of Toll/1L-1 receptor domain-containing adaptor molecule-1 in response to dsRNA (2007)
  • Author(s): Funami K., M. Sasai, Y. Ohba, H. Oshiumi, T. Seya, M. Matsumoto.
  • Journal Title: J Immunol. 179 Pages: 6867-6872
• [Journal Article] Recombinant IL-12/IL-18 antitumor therapy in a guinea pig hepatoma cell implanted model (2007)
  • Author(s): Shiratori, I., Y. Suzuki, H. Oshiumi, N. A. Begum, T. Ebihara, M. Matsumoto, K. Hazeki, K. Kodama, Y. Kashiwazaki, T. Seya.
  • Journal Title: Cancer Sci. 98 Pages: 1936-1942
• [Journal Article] Lipoteichoic acid down-regulates Fce receptor I expression on human mast cells through Toll-like receptor 2 (2007)
  • Author(s): Yoshioka, M., N. Fukuishi, S. Iriguchi, K. Ohsaki, H. Yamanobe, A. Inukai, D. Kurihara, N. Imajo, Y. Yasui, N. Matsui, T. Tsujita, A. Ishii, T. Seya, M. Takahama, M. Akagi.
  • Journal Title: J. Aller. Clin. Immunol. 120 Pages: 452-461
• [Journal Article] Tumor immunotherapy using bone marrow-derived dendritic cells overexpressing Toll-like receptor adaptors (2007)
  • Author(s): Akazawa T., M. Sasai, T. Ebihara, M, Shingai, N. Inoue, M. Matsumoto, T. Seya.
  • Journal Title: FEBS Lett. 581 Pages: 3334-3340
• [Journal Article] C-terminal LRRs of human Toll-like receptor 3 control receptor dimerization and signal transmission (2007)
  • Author(s): Takada, E., S. Okahira, M. Sasai, K. Funami, T. Seya, M. Matsumoto.
  • Journal Title: Molec. Immunol. 44 Pages: 3633-3640
• [Journal Article] Differential type I interferon (IFN) inducing abilities of wild-type vs. vaccine strains of measles virus (2007)
  • Author(s): Shingai, M., T. Ebihara, N. A. Begum, A. Kato,, T. Honma, K. Matsumoto, H. Saito, H. Ogura, M. Matsumoto, T Seya.
  • Journal Title: J. Immunol. 179 Pages: 6123-6133
• [Journal Article] Antitumor NK activation induced by the Toll-like receptor3-TICAM-1 (TRIF) pathway in myeloid dendritic cells (2007)
  • Author(s): Akazawa T., M. Okuno, Y. Okuda, K. Tsujimura, T. Takahashi, M. Ikawa, M. Okabe, T. Ebihara, M, Shingai, N. Inoue, M. Tanaka-Okamoto, H. Ishizaki, J. Miyoshi, M. Matsumoto, T. Seya.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 104 Pages: 252-257
• [Journal Article] Toll-like receptor 3-mediated synthesis and release of eotaxin-1/CCL11 from human bronchial smooth muscle cells stimulated with double-stranded RNA (2007)
  • Author(s): Niimi, K. K. Asano, Y. Shiraishi, T. Nakajima, M. Wakaki, J. Kagyo, T. Takihara, Y. Suzuki, K. Fukunaga, T. Shiomi, T. Ogumal, K. Sayama, K. Yamaguchi, Y. Natori, M. Matsumoto, T. Seya, M. Yamata, A. Ishizaka.
  • Journal Title: J. Immunol. 178 Pages: 489-495
• [Journal Article] Lamprey Toll-like receptors with properties distinct from those of variable lymphocyte receptors (2007)
  • Author(s): Ishii, A., A. Matsuo, H. Sawa, T. Tsujita, K. Shida, M. Matsumoto, T. Seya.
  • Journal Title: J. Immunol. 178 Pages: 397-406
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  • URL: http://www.hucc.hokudai.ac.jp/~e20536/