Homeostatic inflammation: Molecular basis and dysregulation

2013 Fiscal Year Final Research Report

• Project Area: Homeostatic inflammation: Molecular basis and dysregulation
• Project/Area Number: 21117001
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAKE Kensuke 東京大学, 医科学研究所, 教授 (60229812)
• Co-Investigator(Kenkyū-buntansha): KAISHO Tsuneyasu 大阪大学, 免疫学フロンティア研究センター, 教授 (60224325) ; MUTA Tatsushi 東北大学, 理学系研究科, 教授 (60222337) ; KURATA Shoichiro 東北大学, 薬学系研究科, 教授 (90221944) ; KURANAGA Erina 理化学研究所, 発生・再生科学総合研究センター, チームリーダー (90376591)
• Co-Investigator(Renkei-kenkyūsha): OGAWA Yoshihiro 東京医科歯科大学, 難治疾患研究所, 教授 (70291424) ; MARU Yoshiro 東京女子医科大学, 医学部, 教授 (00251447)
• Project Period (FY): 2009-07-23 – 2014-03-31
• Keywords: 自然免疫 / Toll様受容体

Research Abstract

Pathogen sensors, which are conserved from flies to humans, senses not only microbial products but also self-derived products (endogenous ligands). The grant project called Homeostatic Inflammation has focused on interaction between pathogen sensors and endogenous ligands from the healthy state to the disease state. This grant contributed to the project by generating genetically engineered mice and monoclonal antibodies to pathogen sensors, and by supporting analyses of mutant mice and flies.

Research Products

• [Journal Article] UNC93B1 is essential for the plasma membrane localization and signaling of Toll-like receptor 5 (2014)
  • Author(s): Huh JW, Shibata T, Hwang M, Kwon EH, Jang MS, Fukui R, Kanno K, Jung DJ, Jang MH, Miyake K, and Kim YM
  • Journal Title: Proc. Natl. Acad. Sci. USA
  • DOI: 10.1073/pnas.1322838111
• [Journal Article] An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing (2013)
  • Author(s): Onji M, Kanno A, Saitoh S, Fukui R, Motoi Y, Shibata T, Matsumoto F, Lamichhane A, Sato S, Kiyono H, Yamamoto K, Miyake K
  • Journal Title: Nat. Commun. Volume: 4 Pages: 1949
  • DOI: 10.1038/ncomms2949
• [Journal Article] Essential role for Toll-like receptor 7 (TLR7)-unique cysteines in intramolecular disulfide bond, proteolytic cleavage, and RNA-sensing (2013)
  • Author(s): Kanno A, Yamamoto C, Onji M, Fukui R, Saitoh SI, Motoi Y, Shibata T, Matsumoto F, Muta T, Miyake K
  • Journal Title: Int Immunol. Volume: 25 Pages: 413-422
  • DOI: 10.1093/intimm/dxt007
• [Journal Article] Enhanced apoptosis by disruption of the STAT3-IκB-ζ signaling pathway in epithelial cells induces Sjogren's syndrome-like autoimmune disease (2013)
  • Author(s): Okuma A, Hoshino K, Ohba T, Fukushi S, Aiba S, Akira S, Ono M, Kaisho T, Muta T
  • Journal Title: Immunity Volume: 38 Pages: 450-460
  • DOI: 10.1016/j.immuni.2012.11.016
• [Journal Article] PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells (2012)
  • Author(s): Shibata T, Takemura N, Motoi Y, Goto Y, Karuppuchamy T, Izawa K, Li X, Akashi-Takamura S, Tanimura N, Kunisawa J, Kiyono H, Akira S, Kitamura T, Kitaura J, Uematsu S, Miyake K
  • Journal Title: Int Immunol. Volume: 24 Pages: 613-623
  • DOI: 10.1093/intimm/dxs068
• [Journal Article] Spi-B is critical for plasmacytoid dendritic cell function and development (2012)
  • Author(s): Sasaki, K. Hoshino, T. Sugiyama, C. Yamazaki, T. Yano, A. Iizuka, H. Hemmi, T. Tanaka, M. Saito, M. Sugiyama, Y. Fukuda, T. Ohta, K. Sato, A. Ainai, T. Suzuki, H. Hasegawa, N. Toyama-Sorimachi, H. Kohara, T. Nagasawa, T. Kaisho
  • Journal Title: Blood Volume: 120 Pages: 4733-4743
  • DOI: 10.1182/blood-2012-06-436527
• [Journal Article] Revised Structure and Synthesis of Celastramycin A, a Potent Innate Immune Suppressor (2009)
  • Author(s): Kikuchi, H., Sekiya, M., Katou, Y., Ueda, K., Kabeya, T., Kurata, S., and Oshima, Y.
  • Journal Title: Organic letters Volume: 11 Pages: 1693-1695
  • DOI: 10.1021/ol2018449
• [Presentation] An Essential role for the N-terminal fragment of Toll-like receptor 9 (2013)
  • Organizer: Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2013-12-12
• [Presentation] Cell surface TLR3 on CD8-positive dendritic cells and an essential role of the cleaved N-fragment of TLR3 ectodomain in polyI : C sensing (2013)
  • Organizer: Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2013-12-12
• [Presentation] Single Stranded RNA adjusts the TLR7/8 response to agonistic base analogues (2013)
  • Organizer: Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2013-12-12
• [Presentation] Essential role for Toll-like receptor 7 (TLR7)-unique cysteines in an intramolecular disulfide bond, proteolytic cleavage and RNA sensing (2013)
  • Organizer: The 78th Meeting of the Japanese Society for Interferon and Cytokine Research (JSICR) and The 21th International Symposium of Macrophage Molecular and Cellular Biology (MMCB)
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2013-05-21
• [Presentation] Differential requirements of CD14 and Lipopolysaccharide binding priotein in Monophosphoryl lipid A-mediated TLR4 activation (2013)
  • Organizer: American Associate of Immunology, Annual meeting
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2013-05-05
• [Presentation] Arf-like GTPase Arl8b drives TLR7 into type I interferon-mediated autoimmunity (2012)
  • Organizer: Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Hyogo, Japan
  • Year and Date: 2012-12-05
• [Presentation] A GTPase driving TLR7 into type I interferon-mediated autoimmunity (2012)
  • Organizer: The 12th Biennial International Endotoxin & Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-23
• [Presentation] Monophosphoryl lipid A activates TLR4 via LPS-Binding Protein-dependent and CD14-independent fashions (2012)
  • Organizer: The 12th Biennial International Endotoxin & Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-23
• [Presentation] PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells (2012)
  • Organizer: The 12th Biennial International Endotoxin & Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-23
• [Presentation] Cell surface TLR1, 2 and 6 showed variety expression patterns but all depends on PRAT4a completely (2012)
  • Organizer: The 12th Biennial International Endotoxin & Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-23
• [Presentation] Roles for proteolytic cleavage of TLR9 in primary immune cells (2012)
  • Organizer: The 12th Biennial International Endotoxin & Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-23
• [Presentation] Detecting endogenous mouse TLR7 by a monoclonal antibody (2012)
  • Organizer: The 12th Biennial International Endotoxin & Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-23
• [Remarks]
  • URL: http://www.shizen-enshow.jp/
• [Patent(Industrial Property Rights)] 炎症性疾患の予防又は治療剤 (2013)
  • Inventor(s): 三宅健介、菅野敦夫、恩地正浩、本井祐二
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願 2013-089575
  • Filing Date: 2013-04-22