Novel regulatory mechanism of B-cell lymphoma

• Project/Area Number: 15K09491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Aichi Medical University
• Principal Investigator: Akashi-Takamura Sachiko 愛知医科大学, 医学部, 教授 (00325599)
• Co-Investigator(Renkei-kenkyūsha): Odkhuu Erdenezaya 愛知医科大学, 医学部, 助教 (40737681)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: MD-1 / RP105 / 脂質受容体 / S1P

Outline of Final Research Achievements

As a new control structure of B cell lymphoma, B-cell activated control by serum protein MD-1 was suggested. Because MD-1 is a lipid binding molecule and it also associates with RP105 inducing B-cell activation, lipid combination and the connection with the B-cell activation are thought about. Further analysis is necessary how the B cell lymphoma tendency is gained in the MD-1 deleted SLE model mouse by the B-cell activation reinforcement through Lipid and the receptor.

Research Products

• [Int'l Joint Research] モンゴル大学(モンゴル)
• [Int'l Joint Research] アイルランド大学(アイルランド)
• [Int'l Joint Research] モンゴル大学(モンゴル)
• [Journal Article] Neutralizing Antibodies Induced by Gene-Based Hydrodynamic Injection Have a Therapeutic Effect in Lethal Influenza Infection (2018)
  • Author(s): Yamazaki Tatsuya、Nagashima Maria、Ninomiya Daisuke、Ainai Akira、Fujimoto Akira、Ichimonji Isao、Takagi Hidekazu、Morita Naoko、Murotani Kenta、Hasegawa Hideki、Chiba Joe、Akashi-Takamura Sachiko
  • Journal Title: Frontiers in Immunology Volume: 9 Pages: 47-47
  • DOI: 10.3389/fimmu.2018.00047
  • Peer Reviewed / Open Access
• [Journal Article] Epithelial membrane protein 3 (Emp3) downregulates induction and function of cytotoxic T lymphocytes by macrophages via TNF-alpha 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: Cell Immunol Volume: 324 Pages: 33-41
  • DOI: 10.1016/j.cellimm.2017.12.001
  • Peer Reviewed / Open Access
• [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 Pages: 1006-1015
  • DOI: 10.1093/glycob/cwx075
  • Peer Reviewed / Open Access
• [Journal Article] Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex. (2017)
  • Author(s): Okamoto N, Mizote K, Honda H, Saeki A, Watanabe Y, Yamaguchi-Miyamoto T, Fukui R, Tanimura N, Motoi Y, Akashi-Takamura S, Kato T, Fujishita S, Kimura T, Ohto U, Shimizu T, Hirokawa T, Miyake K, Fukase K, Fujimoto Y, Nagai Y, Takatsu K
  • Journal Title: J Biol Chem Volume: 292 Pages: 15378-15394
  • DOI: 10.1074/jbc.m117.791780
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] C4b-binding protein negatively regulates TLR4/MD-2 response but not TLR3 response (2017)
  • Author(s): Morita Naoko、Yamazaki Tatsuya、Murakami Yusuke、Fukui Ryutaro、Yamai Ikuko、Ichimonji Isao、Nakashima Akina、Nagaoka Fumiaki、Takagi Hidekazu、Miyake Kensuke、Akashi-Takamura Sachiko
  • Journal Title: FEBS Letters Volume: 591 Pages: 1732-1741
  • DOI: 10.1002/1873-3468.12693
  • Peer Reviewed
• [Journal Article] C4b binding protein negatively regulates TLR1/2 response (2017)
  • Author(s): Naoko Morita, Ikuko Yamai, Koichiro Takahashi,Yutaka Kusumoto, Takuma Shibata, Toshihiko Kobayashi, Mayumi I Nonaka, Isao Ichimonji, Hidekazu Takagi, Kensuke Miyake and Sachiko A Takamura.
  • Journal Title: Innate Immunity Volume: 23 Pages: 11-19
  • DOI: 10.1177/1753425916672312
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Inflammatory responses increase secretion of MD-1 protein. (2016)
  • Author(s): Thomas Jennings R, Odkhuu E, Nakashima A, Morita N, Kobayashi T, Yamai I, Tanaka M, Suganami T, Haga S, Ozaki M, Watanabe Y, Nagai Y, Takatsu K, Kikuchi-Ueda T, Ichimonji I, Ogawa Y, Takagi H, Yamazaki T, Miyake K, Akashi-Takamura S
  • Journal Title: Int Immunol Volume: 28 Pages: 503-512
  • DOI: 10.1093/intimm/dxw031
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Delayed liver regeneration in C3H/HeJ mice: possible involvement of haemodynamic and structural changes in the hepatic microcirculation (2016)
  • Author(s): Marlini M, Mabuchi A, Mallard BL, Hairulhisyam N, Akashi-Takamura S, Harper JL, Wheatley AM
  • Journal Title: Experimental Physiology Volume: 101 Pages: 1492-1505
  • DOI: 10.1113/ep085727
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Eritoran inhibits S100A8-mediated TLR4/MD-2 activation and tumor growth by changing the immune microenvironment (2016)
  • Author(s): Deguchi A, Tomita T, Ohto U, Takemura K, Kitao A, Akashi-Takamura, S, Miyake K, and Maru Y.
  • Journal Title: Oncogene Volume: 35 Pages: 1445-1456
  • DOI: 10.1038/onc.2015.211
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Inflammatory responses increase secretion of MD-1 protein (2017)
  • Author(s): Sachiko Akashi Takamura, Jennings Thomas Richard, Odkhoo Erdenezaya, Akina Nakashima, Naoko Morita, Toshihiko Kobayashi, Miyako Tanaka, Takayoshi Suganami, Sanae Haga, Yoshinori Nagai, Kensuke Miyake
  • Organizer: 第19回武田科学振興財団生命科学シンポジウム 慢性炎症・機序と制御
  • Place of Presentation: 大阪 武田科学振興財団
  • Year and Date: 2017-01-20
• [Presentation] 補体制御因子 C4BP は TLR4/MD-2 応答も制御する (2017)
  • Author(s): 高村祥子、森田奈央子、山崎達也
  • Organizer: 日本エンドトキシン・自然免疫研究会
• [Presentation] インフルエンザウイルス感染に対する中和抗体遺伝子を用いた治療法の検討 (2017)
  • Author(s): 山崎達也、千葉 丈 、高村（赤司）祥子
  • Organizer: 日本エンドトキシン・自然免疫研究会
• [Presentation] C4b binding protein negatively regulates cell-surface TLRs response (2017)
  • Author(s): Sachiko Akashi-Takamura, Naoko Morita, Tatsuya Yamazaki, Isao Ichimonji, Yusuke Murakami, Ryutaro Fukui, Takuma Shibata, Toshihiko Kobayashi, Yutaka Kusumoto, Kensuke Miyake
  • Organizer: 日本免疫学会学術集会
• [Presentation] Neutralizing antibodies induced by gene-base hydrodynamic injection have a therapeutic effect in nasal influenza virus infection (2017)
  • Author(s): Tatsuya Yamazaki, Akira Ainai, Isao Ichimonji, Naoko Morita, Sachiko Akashi-Takamura
  • Organizer: 日本免疫学会学術集会
• [Presentation] Novel antibodies detect the increased level of soluble MD-1 during inflammation (2016)
  • Author(s): Akashi-Takamura Sachiko, Jennings Richard, Nakashima Akina, Motita Naoko, Kobayashi Toshihiko, Watanabe Yasuharu, Nagai Yoshinori, Takatsu Kiyoshi, Kikuchi-Ueda Takane, Ichimonji Isao, Takagi Hidekazu, Yamazaki Tatsuya, Miyake Kensuke
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2016-12-05
• [Presentation] Antibody-based immunotherapy with plasmid vector for influenza virus infection (2016)
  • Author(s): Yamazaki Tatsuya, Ainai Akira, Akashi-Takamura Sachiko
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2016-12-05
• [Presentation] Regulatory roles against sphingosine-1-phosphate activity via MD-1 (2016)
  • Author(s): Tanimura Natsuko, Takamura Sachiko, Miyake Kensuke
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2016-12-05
• [Presentation] Agonistic effects of synthetic derivatives of funiculosin on mouse/human TLR4/MD-2 (2016)
  • Author(s): Okamoto Naoki, Honda Hiroe, Akashi-Takamura Sachiko,Nagai Yoshinori, Takatsu Kiyoshi
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2016-12-05
• [Presentation] Novel antibodies detect the increased level of soluble MD-1 during inflammation (2016)
  • Author(s): Sachiko Akashi-Takamura
  • Organizer: 第22回日本エンドトキシン・自然免疫研究会
  • Place of Presentation: 鹿児島大学
  • Year and Date: 2016-12-02
• [Presentation] MD-1 is a valuable biomarker for inflammatory responses (2016)
  • Author(s): Richard Thomas Jennings, Erdenezaya Odkhuu, Kensuke Miyake, and Sachiko Akashi-Takamura、et al.
  • Organizer: Keystone Symposia Q7&Q8 (Immunometabolism in Immune Function and Inflammatory Disease)
  • Place of Presentation: Canada Banff
  • Year and Date: 2016-02-23
  • Int'l Joint Research
• [Presentation] 補体系制御因子C4BPはTLR2応答も制御する (2015)
  • Author(s): 森田奈央子、高村（赤司）祥子
  • Organizer: 第21回日本エンドトキシン・自然免疫研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-12-05
• [Presentation] C4b-binding protein influences TLR2 response (2015)
  • Author(s): Naoko Morita, Eredenezaya Odkhoo, Isao Ichimonji, Kensuke Miyake, Sachiko Akashi-Takamura
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] MD-1 negatively regulates B cell-related inflammation (2015)
  • Author(s): Natsuko Tanimura, Sachiko Akashi-Takamura, Natsuko Yamakawa and Kensuke Miyake
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Book] エンドトキシン・自然免疫研究会20自然免疫における化学生物学の貢献 (2017)
  • Author(s): 一文字 功、高村（赤司）祥子
  • Total Pages: 82
  • Publisher: 医学図書出版株式会社
  • ISBN: 9784865171938
• [Book] エンドトキシン・自然免疫研究19 新たなる基礎と臨床の架け橋 (2016)
  • Author(s): 森田奈央子、高村（赤司）祥子
  • Total Pages: 5
  • Publisher: 医学図書出版株式会社
• [Remarks] 愛知医科大学 医学部 感染・免疫学講座２
  • URL: http://www.aichi-med-u.ac.jp/M-I2/index.html
• [Remarks] 愛知医科大学感染免疫学講座・免疫寄生虫学教室
  • URL: http://www.aichi-med-u.ac.jp/M-I2/index.html