Analysis of the mechanism for controlling reciprocal balance in nucleic acid sensing-innate immune system

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790454
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: FUKUI Ryutaro 東京大学, 医科学研究所, 特任助教 (60554508)
• Project Period (FY): 2010 – 2011
• Keywords: 自然免疫 / Toll-like receptor / Unc93 homolog B1 / 自然炎症 / サイトカイン / 内因性リガンド / 新規分子探索 / 肝炎

Research Abstract

We generated Unc93b1D34A/D34A mutant mouse to analyze the significance of reciprocal TLR7/TLR9 balance in vivo. As results, various phenotypes were developed in these mice spontaneously and over half of mice died within 1 year because of TLR7 hyper-response. For example, hepatitis, splenomegaly, thrombocytopenia, and glomerulonephritis were observed. From these results, it is confirmed that reciprocal TLR7/TLR9 balance is an essential mechanism for avoiding lethal homeostatic inflammation.

Research Products

• [Journal Article] Unc93B1 Restricts Systemic Lethal Inflammation by Orchestrating Toll-like Receptor 7 and 9 Trafficking. (2011)
  • Author(s): Ryutaro Fukui, Shin-Ichiroh Saitoh, Atsuo Kanno, Masahiro Onji, Takuma Shibata, Akihiko Ito, Morikazu Onji, Mitsuru Matsumoto, Shizuo Akira, Nobuaki Yoshida, and Kensuke Miyake
  • Journal Title: Immunity 35 Pages: 1-13
  • Peer Reviewed
• [Presentation] Unc93 homolog B1 restricts systemic lethal inflammation by orchestrating TLR7 and TLR9 response (2011)
  • Author(s): Ryutaro Fukui, Shin-Ichiroh Saitoh, Atuso Kanno, Masahiro Onji, Takuma Shibata, Akihiko Ito, Shizuo Akira, Nobuaki Yoshida, and Kensuke Miyake
  • Organizer: TOLL2011
  • Place of Presentation: Rivadel Garda, Italy
  • Year and Date: 20110504-07
• [Presentation] Unc93 homolog B1restricts lethal homeostatic inflammation by regulating TLR7 and TLR9 reciprocally (2011)
  • Author(s): Ryutaro Fukui, Shin-Ichiroh Saitoh, Atuso Kanno, Masahiro Onji, Takuma Shibata, Akihiko Ito, Morikazu Onji, Mitsuru Matsumoto, Shizuo Akira, Nobuaki Yoshida, and Kensuke Miyake
  • Organizer: 第40回日本免疫学会学術集会ワークショップ
  • Place of Presentation: 幕張メッセ,千葉県
  • Year and Date: 2011-11-28
• [Presentation] Unc93 homolog B1 restricts systemic lethal inflammation by or chestrating TLR7 and TLR9 response (2011)
  • Author(s): Ryutaro Fukui
  • Organizer: Bio-Rheumatology International Congress(BRIC) Tokyo, The 8th GARN Meeting
  • Place of Presentation: ヒルトン東京ベイホテル,千葉県
  • Year and Date: 2011-11-14
• [Presentation] Roles for Unc93 homologB1-dependent TLR7/TLR9 balance invivo (2010)
  • Author(s): Ryutaro Fukui, Shin-ichiroh Saitoh, Masahiro Onji, Takuma Shibata, Akihiko Ito, Keiko B. Kimura, Nobuaki Yoshida, Kensuke Miyake
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-23