Elusidation of regulatory mechanism for regulatory Tcells by Arl8b

• Project/Area Number: 16K15253
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: Saitoh Shin-Ichiroh 東京大学, 医科学研究所, 准教授 (90361625)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 全身性エリトマトーデス / Toll-like receptor 7 / 自己免疫疾患 / Arl8b / 全身性エリテマトーデス / 低分子量Gタンパク質 / 制御性T細胞 / 免疫制御

Outline of Final Research Achievements

I revealed that a small G protein Arl8b is associated with TLR7 and regulates TLR7 function. So, I analyzed several SLE mouse models. In some SLE mouse models, I analyzed the role of Arl8b on MRL/lpr mouse model. I observed that Arl8b plays an essential role for the development of SLE in this model. Because MRL/lpr mouse model is not much dependent on TLR7 function, I analyzed carefully TLR7 independent mechanism. I observed that regulatory T cells significantly increased in spleen of MRL/lpr Arl8b deficient mice compared with MRL/lpr wild type mice. IL-2 controls regulatory T cells. I observed IL-2 receptor expression level in spleen of MRL/lpr Arl8b deficient mouse. I found that IL-2 receptor expression level is significantly high on MRL/lpr Arl8b deficient T cells. I will analyze the role of Arl8b for IL-2 receptor expression and controlling regulatory T cell.

Research Products

• [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] Epithelial membrane protein 3 (Emp3) downregulates induction and function of cytotoxic T lymphocytes by macrophages via TNF-α production (2018)
  • Author(s): Kusumoto Yutaka、Okuyama Hiromi、Shibata Takuma、Konno Kazunori、Takemoto Yusuke、Maekawa Daisuke、Kononaga Tomoyuki、Ishii Takashi、Akashi-Takamura Sachiko、Saitoh Shin-ichiroh、Ikebuchi Ryoyo、Moriya Taiki、Ueda Mizuki、Miyake Kensuke、Ono Shiro、Tomura Michio
  • Journal Title: Cellular Immunology Volume: 324 Pages: 33-41
  • DOI: 10.1016/j.cellimm.2017.12.001
  • 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] 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] Core fucose is critical for CD14-dependent Toll-like receptor 4 signaling (2017)
  • Author(s): 4.Iijima J, Kobayashi S, Kitazume S*, Kizuka Y, Fujinawa R, Korekane H, Shibata T, Saitoh S, Akashi-Takamura S, Miyake K, Miyoshi E, and Taniguch N
  • Journal Title: Glycobiology Volume: 2017 Issue: 11 Pages: 1006-1015
  • DOI: 10.1093/glycob/cwx075
  • Peer Reviewed / Open Access
• [Journal Article] Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm of mouse embryos (2017)
  • Author(s): Oka M, Hashimoto K, Yamaguchi Y, Saitoh SI, Sugiura Y, Motoi Y, Honda K, Kikko Y, Ohata S, Suematsu M, Miura M, Miyake K, Katada T and Kontani K
  • Journal Title: J Cell Sci Volume: 130 Issue: 20 Pages: 3568-3577
  • DOI: 10.1242/jcs.200519
  • Peer Reviewed / Open Access
• [Presentation] Arl8bは全身性エリテマトーデスモデルマウスBXSB.Yaaの病気の発症に関わっている. (2017)
  • Author(s): 齋藤 伸一郎
  • Organizer: 第23回日本エンドトキシン・自然免疫研究会
• [Presentation] ADP-ribosylation factor-like 8b is required for the pathogenesis of mouse models of Systemic Lupus Erythematosus. (2017)
  • Author(s): Shin-Ichiroh Saitoh, Yoshiko Mori Saitoh, Katsuaki Sato, Kenji Kontani, and Kensuke Miyake
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] Metabolic permission for IFNa induction is connected by Toll-like Receptor 7 trafficking (2016)
  • Author(s): Shin-Ichiroh Saitoh
  • Organizer: 日本免疫学会
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2016-12-05
  • Invited
• [Presentation] Toll-like receptor 7の移動は代謝センサーmTorC1による1型インターフェロン産生の制御と結びついている (2016)
  • Author(s): 齋藤 伸一郎
  • Organizer: 日本エンドトキシン・自然免疫研究会
  • Place of Presentation: 鹿児島大学 郡元キャンパス
  • Year and Date: 2016-12-02
• [Book] エンドトキシン・自然免疫２０ (2017)
  • Author(s): 齋藤 伸一郎
  • Total Pages: 3
  • Publisher: 日本エンドトキシン・自然免疫研究会
• [Remarks] 東京大学医科学研究所 感染遺伝学
  • URL: http://www.ims.u-tokyo.ac.jp/kanseniden/
• [Remarks] 医科学研究所Annual report
  • URL: http://www.ims.u-tokyo.ac.jp/imsut/jp/about/publication/annualreport/
• [Remarks] 東京大学医科学研究所Annual report
  • URL: http://www.ims.u-tokyo.ac.jp/imsut/jp/about/publication/annualreport/
• [Remarks] 東京大学医科学研究所 感染遺伝学ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/kanseniden/index.html