Understanding a mechanism controlling endogenous retrovirus by Toll-like receptors

• Project/Area Number: 17K19548
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAKE Kensuke 東京大学, 医科学研究所, 教授 (60229812)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 自然免疫 / Toll様受容体 / 免疫学

Outline of Final Research Achievements

Activation of endogenous retroviruses (ERVs) is controlled by nucleic acid-specific Toll-like receptors. This study focused on molecular mechanisms behind ERV activation and TLR7 responses to ERVs. We found that the lack of a single gene increased expression of ERVs and activated TLR7 and.

Academic Significance and Societal Importance of the Research Achievements

内在性レトロウイルスは、ゲノムにコードされているにも関わらず、外来性のウイルスと同じように核酸特異的Toll様受容体（Toll-like receptor, TLR）に認識されることが分かっている。核酸特異的TLRがないと、内在性レトロウイルスが活性化されてしまう。本研究では、内在性レトロウイルスの制御機構とTLR7の活性化の関係について検討した。本研究の結果は、内在性レトロウイルスの制御機構の解明に貢献しうる。

Research Products

• [Journal Article] ADP-ribosylation factor-like 8b is required for the development of mouse models of systemic lupus erythematosus (2019)
  • Author(s): Saitoh Shin-Ichiroh、Saitoh Yoshiko Mori、Kontani Kenji、Sato Katsuaki、Miyake Kensuke
  • Journal Title: International Immunology Volume: 31 Issue: 4 Pages: 225-237
  • DOI: 10.1093/intimm/dxy084
  • Peer Reviewed / Open Access
• [Journal Article] Cytidine deaminase enables Toll-like receptor 8 activation by cytidine or its analogs. (2019)
  • Author(s): Furusho K, Shibata T, Sato R, Fukui R, Motoi Y, Zhang Y, Saitoh SI, Ichinohe T, Moriyama M, Nakamura S, Miyake, K.
  • Journal Title: International immunology. Volume: 31 Issue: 3 Pages: 167-173
  • DOI: 10.1093/intimm/dxy075
  • Peer Reviewed / Open Access
• [Journal Article] Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis. (2018)
  • Author(s): Sato R, Kato A, Chimura T, Saitoh SI, Shibata T, Murakami Y, Fukui R, Liu K, Zhang Y, Arii J, Sun-Wada GH, Wada Y, Ikenoue T, Barber GN, Manabe T, Kawaguchi Y, Miyake K.
  • Journal Title: Nat Immunol. Volume: 19 Issue: 10 Pages: 1071-1082
  • DOI: 10.1038/s41590-018-0203-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mechanisms controlling nucleic acid-sensing Toll-like receptors (2018)
  • Author(s): Miyake Kensuke、Shibata Takuma、Ohto Umeharu、Shimizu Toshiyuki、Saitoh Shin-Ichiroh、Fukui Ryutaro、Murakami Yusuke
  • Journal Title: International Immunology Volume: 30 Issue: 2 Pages: 43-51
  • DOI: 10.1093/intimm/dxy016
  • Peer Reviewed / Open Access
• [Journal Article] TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells (2017)
  • Author(s): Saitoh SI, Abe F, Kanno A, Tanimura N, Mori Saitoh Y, Fukui R, Shibata T, Sato K, Ichinohe T, Hayashi M, Kubota K, Kozuka-Hata H, Oyama M, Kikko Y, Katada T, Kontani K and Miyake K
  • Journal Title: Nat Commun Volume: 8 Issue: 1 Pages: 1592-1592
  • DOI: 10.1038/s41467-017-01687-x
  • Peer Reviewed / Open Access
• [Journal Article] Requirement of glycosylation machinery in TLR responses revealed by CRISPR/Cas9 screening (2017)
  • Author(s): Sato Ryota、Shibata Takuma、Tanaka Yu、Kato Chiharu、Yamaguchi Kiyoshi、Furukawa Yoichi、Shimizu Eigo、Yamaguchi Rui、Imoto Seiya、Miyano Satoru、Miyake Kensuke
  • Journal Title: International Immunology Volume: 29 Issue: 8 Pages: 347-355
  • DOI: 10.1093/intimm/dxx044
  • Peer Reviewed / Open Access
• [Journal Article] The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA (2017)
  • Author(s): Murakami Y, Fukui R, Motoi Y, Shibata T, Saitoh SI, Sato R, Miyake K.
  • Journal Title: Scientific Report Volume: 7 Issue: 1 Pages: 44042-44054
  • DOI: 10.1038/srep44042
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Selectivity of Human TLR9 for Double CpG Motifs and Implications for the Recognition of Genomic DNA (2017)
  • Author(s): Pohar J, Yamamoto C, Fukui R, Cajnko MM, Miyake K, Jerala R, Bencina M
  • Journal Title: J Immunol Volume: 198 Issue: 5 Pages: 2093-2104
  • DOI: 10.4049/jimmunol.1600757
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Mechanism controlling TLR7 and their regulation in diseases (2018)
  • Author(s): Kensuke Miyake
  • Organizer: International Union of Biochemistry and Molecular Biology 2018 (IUBMB2018)
  • Int'l Joint Research / Invited
• [Presentation] Mechanism controlling TLR7 and their regulation in diseases (2018)
  • Author(s): Kensuke Miyake
  • Organizer: 51st annual meeting of the society for leukocyte biology and 15th biennial meeting of the international endotoxin and innate immunity society
  • Int'l Joint Research / Invited
• [Presentation] Mechanism controlling TLR7 and their regulation in diseases (2018)
  • Author(s): Kensuke Miyake
  • Organizer: The 9th Asian congress of pediatric infectious diseases
  • Int'l Joint Research / Invited
• [Presentation] Mechanism controlling TLR7 and their regulation in diseases (2018)
  • Author(s): Kensuke Miyake
  • Organizer: The 47th annual meeting of the Japanese society for immunology
  • Int'l Joint Research / Invited