Molecular mechanisms of dendritic cell maturation in response to pattern sensing

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390120
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Hokkaido University
• Principal Investigator: SEYA Tsukasa 北海道大学, 医学(系)研究科(研究院), 教授 (10301805)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Misako 北海道大学, 大学院・大医学研究科, 准教授 (30332456) ; OSHIUMI Hiroyuki 北海道大学, 大学院・大医学研究科, 講師 (50379103) ; SHIME Hiroaki 北海道大学, 大学院・大医学研究科, 助教 (70372133)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 自然免疫 / Toll-like receptor / 樹状細胞 / TICAM-1 / IPS-1

Research Abstract

RNA virus response results in induction of type I interferon (IFN) and cellular immunity. Type I IFN is a pivotal factor for host cell protection against acute viral infection, whereas dendritic cells (DC), consisting of multiple subsets, induce variable responses against chronic viral infections. CD8a+ DC express high levels of TLR3 and represent cross-presentation of exogenous antigens. They also induce NK cell activation against viruses. Viral RNA is taken up into the endosome where TLR3 is situated in CD8a+ DC. TLR3 is profoundly involved in the step of CTL induction, namely cross-priming. The presence of multifarious RNA sensors reflects the variation of viral species, each of which behaves differentially to survive in the host. A variety of antiviral immune response reflects the presence of RNA sensors covering RNAs with virus-to-virus differences in various host cells.

Research Products

• [Journal Article] IPS-1 Is Essential for Type III IFN Production by Hepatocytes and Dendritic Cells in Response to Hepatitis C Virus Infection (2014)
  • Author(s): Okamoto M, Oshiumi H, Azuma M, Kato N, Matsumoto M, Seya T
  • Journal Title: J Immunol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Beyond dsRNA : Toll-like receptor 3 signalling in RNA-induced immune responses (2014)
  • Author(s): Tatematsu M, Seya T, Matsumoto M
  • Journal Title: Biochem J Volume: 458(2) Pages: 195-201
  • Peer Reviewed
• [Journal Article] MAVS-dependent IRF3/7 bypass of interferon β-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells (2014)
  • Author(s): Takaki H, Honda K, Atarashi K, Kobayashi F, Ebihara T, Oshiumi H, Matsumoto M, Shingai M, Seya T
  • Journal Title: Mol Immunol Volume: 57(2) Pages: 100-10
  • Peer Reviewed
• [Journal Article] Myeloid-derived suppressor cells confer tumor-suppressive functions on natural killer cells via polyinosinic : polycytidylic acid treatment in mouse tumor models (2014)
  • Author(s): Shime H, Kojima A, Maruyama A, Saito Y, Oshiumi H, Matsumoto M, Seya T
  • Journal Title: J Innate Immun Volume: 6 Pages: 293-305
  • Peer Reviewed
• [Journal Article] Assessment of the Toll-like receptor 3 pathway in endosomal signaling (2014)
  • Author(s): Matsumoto M, Funami K, Tatematsu M, Azuma M, Seya T
  • Journal Title: Methods Enzymol Volume: 535 Pages: 149-65
  • Peer Reviewed
• [Journal Article] Cell type-specific subcellular localization of phospho-TBK1 in response to cytoplasmic viral DNA (2013)
  • Author(s): Suzuki T, Oshiumi H, Miyashita M, Aly HH, Matsumoto M, Seya T
  • Journal Title: PLoS One Volume: 8(12) Pages: e83639
  • Peer Reviewed
• [Journal Article] Structures and interface mapping of the TIR domain-containing adaptor molecules involved in interferon signaling (2013)
  • Author(s): Enokizono Y, Kumeta H, Funami K, Horiuchi M, Sarmiento J, Yamashita K, Standley DM, Matsumoto M, Seya T, Inagaki F
  • Journal Title: Proc Natl Acad Sci USA Volume: 110(49) Pages: 19908-13
  • Peer Reviewed
• [Journal Article] The MyD88 pathway in plasmacytoid and CD4+ dendritic cells primarily triggers type I IFN production against measles virus in a mouse infection model (2013)
  • Author(s): Takaki H, Takeda M, Tahara M, Shingai M, Oshiumi H, Matsumoto M, Seya T
  • Journal Title: J Immunol Volume: 191(9) Pages: 4740-7
  • Peer Reviewed
• [Journal Article] A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses (2013)
  • Author(s): Oshiumi H, Miyashita M, Matsumoto M, Seya T
  • Journal Title: PLoS Pathog Volume: 9(8) Pages: e1003533
  • Peer Reviewed
• [Journal Article] Herpesvirus 6 glycoproteins B (gB), gH, gL, and gQ are necessary and sufficient for cell-to-cell fusion (2013)
  • Author(s): Tanaka Y, Suenaga T, Matsumoto M, Seya T, Arase H.
  • Journal Title: J Virol Volume: 87(19) Pages: 10900-3
  • Peer Reviewed
• [Journal Article] Hepatitis C virus infection induces inflammatory cytokines and chemokines mediated by the cross talk between hepatocytes and stellate cells (2013)
  • Author(s): Nishitsuji H, Funami K, Shimizu Y, Ujino S, Sugiyama K, Seya T, Takaku H, Shimotohno K
  • Journal Title: J Virol Volume: 87 Pages: 8169-78
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA (2013)
  • Author(s): Tatematsu M, Nishikawa F, Seya T, Matsumoto M
  • Journal Title: Nat Commun Volume: 4 Pages: 1833
  • Peer Reviewed
• [Journal Article] Targeting TLR3 with no RIG-I/MDA5 activation is effective in immunotherapy for cancer (2013)
  • Author(s): Seya T, Azuma M, Matsumoto M
  • Journal Title: Expert Opin Ther Targets Volume: 17(5) Pages: 533-44
  • Peer Reviewed
• [Journal Article] Multi-step regulation of interferon induction by hepatitis C virus (2013)
  • Author(s): Oshiumi H, Funami K, Aly HH, Matsumoto M, Seya T
  • Journal Title: Arch Immunol Ther Exp (Warsz) Volume: 61(2) Pages: 127-38
  • Peer Reviewed
• [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
  • Journal Title: J Immunol Volume: 190(2) Pages: 764-73
  • Peer Reviewed
• [Journal Article] TLR3/TICAM-1 signaling converts tumor-supporting myeloid cells to tumoricidal effectors (2012)
  • Author(s): Shime H, M. Matsumoto, H. Oshiumi, S. Tanaka, A. Nakane, Y. Iwakura, H. Tahara, N. Inoue, and T. Seya
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Pages: 2066-2071
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3-mediated antivirus response is important for protection against poliovirus infection in poliovirus receptor transgenic mice (2012)
  • Author(s): Abe, Y., K. Fujii, N. Nagata, O. Takeuchi, S. Akira, H. Oshiumi, M. Matsumoto, T. Seya, and S. Koike
  • Journal Title: J. Virol Volume: 86 Pages: 185-194
  • Peer Reviewed
• [Journal Article] Dendritic cells from oral cavity induce Foxp3+ regulatory T cells upon antigen stimulation (2012)
  • Author(s): Yamazaki, S., A. Maruyama, K. Okada, M. Matsumoto, A. Morita, and T. Seya
  • Journal Title: PLoS ONE Volume: 7 Pages: e51665
  • Peer Reviewed
• [Journal Article] The SKI2-related helicase DDX60 is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling (2011)
  • Author(s): Miyashita, M., H. Oshiumi, M. Matsumoto, and T. Seya
  • Journal Title: Molec. Cell. Biol Volume: 31 Pages: 3802-3819
  • Peer Reviewed
• [Journal Article] Natural killer cells recognize Friend retrovirus infected erythroid progenitor cells through NKG2D-RAE-1 interactions in vivo (2011)
  • Author(s): Ogawa, T., S. Tsuji-Kawahara, T. Yuasa, S. Kinoshita, T. Chikaishi, S. Takamura, H. Matsumura, T. Seya, T. Saga, and M. Miyazawa
  • Journal Title: J. Virol Volume: 85 Pages: 5423-5435
  • Peer Reviewed
• [Journal Article] Raftlin is involved in the nucleocapture complex to induce poly(I : C)-mediated TLR3 activation (2011)
  • Author(s): Watanabe, A., M. Tatematsu, K. Saeki, S. Shibata, H. Shime, A. Yoshimura, C. Obuse, T. Seya, and M. Matsumoto
  • Journal Title: J. Biol. Chem Volume: 86 Pages: 10702-10711
  • Peer Reviewed
• [Journal Article] Establishing mouse hepatoma cell lines permissive to human hepatitis C virus (2011)
  • Author(s): Aly, H. H., H. Oshiumi, M. Matsumoto, K. Shimotohno, T. Wakita, and T. Seya
  • Journal Title: PLoS ONE Volume: 6 (6) Pages: e21284
  • Peer Reviewed
• [Journal Article] The TLR3-TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection (2011)
  • Author(s): Oshiumi, H., M. Okamoto, K. Fujii, T. Kawanishi, M. Matsumoto, S. Koike, and T. Seya
  • Journal Title: J. Immunol Volume: 187 Pages: 5320-5327
  • Peer Reviewed
• [Journal Article] Phosphoinositide 3-kinase<gamma> controls the intracellular localization of CpG to limit DNA-PKcs-dependent IL-10 production in macrophages (2011)
  • Author(s): Hazeki, K., Y. Kametani, H. Murakami, M. Uehara, K. Nigorokawa, S. Takasuga, T. Sasaki, M. Matsumoto, T. Seya, and O. Hazeki
  • Journal Title: PLoS ONE Volume: 6(10) Pages: e26836
  • Peer Reviewed
• [Journal Article] UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling (2011)
  • Author(s): Itoh, H., A. Watanabe, K. Iwano, K. Funami, T. Seya, and M. Matsumoto
  • Journal Title: PLoS ONE Volume: 6(12) Pages: e28500
  • Peer Reviewed
• [Journal Article] Human TRIF deficiency in otherwise healthy patients with herpes simplex encephalitis (2011)
  • Author(s): Sancho-Shimizu, V., R. Pérez de Diego, L. Lorenzo, R. Halwani, A. Alangari, S. Fabrega, A. Cardon, J. Maluenda, M. Tatematsu, F. Mahvelati, M. Herman, M. Ciancanelli, Y. Guo, A. Ghadiri, S. Boucheriti, S. Plancoulaine, C. Picard, F. Rosenberg, M. Tardieu, P. Lebon, E. Jouanguy, T. Seya, M. Matsumoto, N. Rezeai, D. Chaussabel, A. Puel, L. Abel, S-Y. Zhang, S. Al-Muhsen, and J-L. Casanova
  • Journal Title: J. Clin. Invest Volume: 121 Pages: 4889-4902
  • Peer Reviewed
• [Journal Article] Antiviral responses induced by the TLR3 pathway (2011)
  • Author(s): Matsumoto, M., H. Oshiumi, and T. Seya
  • Journal Title: Rev. Med. Virol Volume: 21 Pages: 67-77
  • Peer Reviewed
• [Journal Article] Will there be an HCV meeting in 2020? : Summary of the 17th International Meeting on Hepatitis C Virus and Related Viruses (2011)
  • Author(s): Wakita, T., T. Suzuki, M. J. Evans, K. Shimotohno, K. Chayama, Y. Matsuura, M. Hijikata, K. Moriishi, T. Seya, N. Enomoto, K. Koike, N. Kato, T. Kanto, and H. Hotta
  • Journal Title: Gastroenterology Volume: 141 Pages: e1-5
  • Peer Reviewed
• [Remarks] HP
  • URL: http://www.hucc.hokudai.ac.jp/~e20536/