The control mechanism of immune response by MD molecules

• Project/Area Number: 23590564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Aichi Medical University (2013-2014); The University of Tokyo (2011-2012)
• Principal Investigator: AKASHI-TAKAMURA Sachiko 愛知医科大学, 医学部, 教授 (00325599)
• Research Collaborator: YAMAKAWA Natsuko
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: MD-1 / 脂質 / B細胞 / RP105 / 脂質レセプター / TLR

Outline of Final Research Achievements

We found that a serum lipid and lipid-receptor induced signal works as an activator of immunology, importantly. A soluble protein MD-1 associated with RP105, which is one of the similar molecules of Toll-like receptors (TLRs) on immune cells. MD-1 was found in serum by our established ELISA assay. We also found the possibility that the serum MD-1 regulated a surplus immune response by a controlling the lipid activation.

Research Products

• [Journal Article] TLR4応答におけるRP105/MD-1の役割 (2014)
  • Author(s): 森田奈央子、高村祥子
  • Journal Title: 臨床免疫・アレルギー科 Volume: 62 Pages: 217-222
• [Journal Article] スフィンゴシン１リン酸の生体における機能について (2014)
  • Author(s): 中島昭奈、高村祥子
  • Journal Title: エンドトキシン・自然免疫研究 Volume: 17 Pages: 49-52
• [Journal Article] 敗血症性ショックに関与するToll-like Receptorの機能 (2014)
  • Author(s): 高村（赤司）祥子
  • Journal Title: 化学療法の領域 Volume: 30 Pages: 40-47
• [Journal Article] Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci (2013)
  • Author(s): Hiratsuka S, Ishibashi S, Tomita T, Watanabe A, Tamura SA, Murakami M, Kijima H, Miyake K, Aburatani H, Maru Y
  • Journal Title: Nat Commun Volume: 4 Issue: 1 Pages: 1853-1853
  • DOI: 10.1038/ncomms2856
  • Peer Reviewed
• [Journal Article] Serum Amyroid A3 binds MD-2 to activates p38 and NF-kB pathway in a MyD88-dependent manner (2013)
  • Author(s): Deguchi A, Tomita T, Omori T, Komatsu A, Ohto U, Takahashi S, Tanimura N, Akashi-Takamura S, Miyake K, Maru Y
  • Journal Title: J Immunol Volume: 191(4) Issue: 4 Pages: 1856-1864
  • DOI: 10.4049/jimmunol.1201996
  • Peer Reviewed
• [Journal Article] Noncanonical inflammasome activation by intracellular LPS independent of TLR4. (2013)
  • Author(s): Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, Miyake K, Zhang J, Lee WP, Muszyński A, Forsberg LS, Carlson RW, Dixit VM.
  • Journal Title: Science. Volume: 341 Issue: 6151 Pages: 1246-9
  • DOI: 10.1126/science.1240248
  • Peer Reviewed
• [Journal Article] The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of TLR4/MD2 complex at the plasma membrane (2013)
  • Author(s): Tanimura N, Saitoh S, Ohto U, Akashi-Takamura A, Fujimoto Y, Fukase K, Shimizu T, Miyake K
  • Journal Title: Int. Immunol. Volume: 26 Issue: 6 Pages: 307-314
  • DOI: 10.1093/intimm/dxt071
  • Peer Reviewed
• [Journal Article] Human TLR4 polymorphism D299G/T399I alters TLR4/MD-2 conformation and response to a weak ligand monophosphoryl lipid A (2013)
  • Author(s): N. Yamakawa, U. Ohto, S. Akashi-Takamura, K. Takahashi, SI. Saitoh, N. Tanimura, T. Suganami, Y. Ogawa, T. Shibata, T. Shimizu, K. Miyake
  • Journal Title: Int. Immunol. Volume: 25 Issue: 1 Pages: 45-52
  • DOI: 10.1093/intimm/dxs084
  • Peer Reviewed
• [Journal Article] TLR4-MD-2 complex is negatively regulated by an endogenous ligand, globotetraosylceramide in vascular endothelial cells. (2013)
  • Author(s): Kondo, Y., Tokuda, N., Nishitani, C., Ohto, U., Akashi-TakKondo, Y., Tokuda, N., Nishitani, C., Ohto, U., Akashi-Takamura, S., Ito, Y., Uchikawa, M., Kuroki, Y., Miyake, K., Zhang, Q., Furukawa, K., Furukawa, K
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 110 Issue: 12 Pages: 4714-4719
  • DOI: 10.1073/pnas.1218508110
  • Peer Reviewed
• [Journal Article] Glycyrrhizin and isoliquiritigenin suppress the LPS sensor Toll-like receptor 4/MD-2 complex signaling in a different manner (2012)
  • Author(s): Honda, H., et al
  • Journal Title: Journal of Leukocyte Biology Volume: (in press) Issue: 6 Pages: 967-976
  • DOI: 10.1189/jlb.0112038
  • Peer Reviewed
• [Journal Article] PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells. (2012)
  • Author(s): Shibata T
  • Journal Title: Int. Immunol. Volume: 10 Pages: 613-23
  • Peer Reviewed
• [Journal Article] Structural analyses of human Toll-like receptor polymorphisms D299G and T399I (2012)
  • Author(s): Ohto U, Yamakawa N, Akashi-Takamura S, Miyake K, Shimizu T
  • Journal Title: J Biol Chem. Volume: 287 Issue: 48 Pages: 40611-40617
  • DOI: 10.1074/jbc.m112.404608
  • Peer Reviewed
• [Journal Article] Coagulation Factor X Activates Innate Immunity to Human Species C Adenovirus. (2012)
  • Author(s): Doronin K.
  • Journal Title: Science. Volume: 6108 Issue: 6108 Pages: 795-8
  • DOI: 10.1126/science.1226625
  • Peer Reviewed
• [Journal Article] Intracellular TLR4/MD-2 in macrophages senses Gram-negative bacteria and induces a unique set of LPS-dependent genes (2011)
  • Author(s): Shibata T, Motoi Y, Tanimura N, Yamakawa N, Akashi-Takamura S, Miyake, K
  • Journal Title: Int.Immunol. Volume: 23 Issue: 8 Pages: 503-510
  • DOI: 10.1093/intimm/dxr044
  • Peer Reviewed
• [Presentation] MD-1 influences a binding between S1P1and BCR (2015)
  • Author(s): Sachiko Akashi-Takamura, Natsuko Yamakawa, Natsuko Tanimura,Takuma Shibata, Kazuhiro Suzuki, Junichi Kikuta, Masaru Ishii, Kensuke Miyake
  • Organizer: 日本細菌学会総会
  • Place of Presentation: 長良川国際会議場（岐阜）
  • Year and Date: 2015-03-26 – 2015-03-28
  • Invited
• [Presentation] The search for endogenous ligands of RP105/MD-1 receptor complex on B cells (2015)
  • Author(s): Erdenezaya Odkhuu, Naoko Morita, Yuji Motoi, Kensuke Miyake, Sachiko Akashi-Takamura
  • Organizer: 4th Bizan Immunology Symposium
  • Place of Presentation: 徳島大学（徳島）
  • Year and Date: 2015-01-29 – 2015-01-30
• [Presentation] MD-1 influences a binding between S1P1and BCR (2014)
  • Author(s): Sachiko Akashi-Takamura, Natsuko Yamakawa,Takuma Shibata, Yosuke Kurashima, Jun Kunisawa, Hiroshi Kiyono, Kazuhiro Suzuki, Junichi Kikuta, Masaru Ishii, Kensuke Miyake
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] The search for endogenous ligand of RP105/MD1 receptor complex on B cell (2014)
  • Author(s): ODKHUU Erdenezaya, MORITA Naoko, MOTOI Yuji, MIYAKE Kensuke, AKASHI-TAKAMURA Sachiko
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Lipopolysaccharide downregulates the expression of p53 through activation of MDM2 and enhances activation of nuclear factor-kappa B (2014)
  • Author(s): Erdenezaya Odkhuu, Adilsaikhan Mendjargal, Naoki Koide, Naoko Morita, Sachiko Akashi-Takamura and Takashi Yokochi
  • Organizer: 日本エンドトキシン・自然免疫研究会
  • Place of Presentation: 順天堂大学（東京）
  • Year and Date: 2014-12-05 – 2014-12-06
• [Presentation] S1P1 IS REQUIRED FOR B CELL RECEPTOR- AND TOLL-LIKE RECEPTOR-MEDIATED
  • Author(s): Sachiko Akashi-Takamura1, Natsuko Yamakawa2, Natsuko Tanimura1, Takuma Shibata1, Takeaki Amiya3,4, Yosuke Kurashima3,4, Jun Kunisawa3 Hiroshi Kiyono4, Kazuhiro Suzuki5, Junichi Kikuta6, Masaru Ishii6, Richard L.Proia7, Yasuo Okamoto8, Yoh Takuwa8, and Kensuke Miyake1
  • Organizer: エンドトキシン・自然免疫研究会
  • Place of Presentation: 滋賀県大津市
• [Presentation] S1P1 is required for B cell activation by B cell receptor or Toll-like receptor
  • Author(s): Sachiko Akashi-Takamura, Natsuko Yamakawa, Natsuko Tanimura, Takuma Shibata, Takeaki Amiya, Yosuke Kurashima, Jun Kunisawa, Hiroshi Kiyono, Kazuhiro Suzuki, Junichi Kikuta, Masaru Ishii, Richard L.Proia, Yoh Takuwa, and Kensuke Miyake
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 千葉県（幕張メッセ）
• [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
  • Author(s): Murakami Yusuke, Yuji Motoi, Shibata Takuma, Fukui Ryutaro, Onji Masahiro, Kanno Atsuo, Yamakawa Natsuko, Takamura Sachiko, Miyake Kensuke
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 千葉県（幕張メッセ）
• [Presentation] 脂質会合分子による自己抗体産生への影響
  • Author(s): 高村（赤司）祥子
  • Organizer: 日本臨床免疫学会
  • Place of Presentation: 京王プラザホテル（新宿）
  • Invited
• [Presentation] Roles for RP105/MD-1in autoantibody production
  • Author(s): Sachiko Akashi-Takamura
  • Organizer: Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: National Center of Science Building (Tokyo)
• [Presentation] Human TLR4 polymorphism D299G/T399I alerts TLR4/MD-2 conformation and response to a weak ligand monophoshoryl lipidA
  • Author(s): Natsuko Yamakawa
  • Organizer: Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: National Center of Science Building (Tokyo)
• [Presentation] Cell surface TLR1, 2 and 6 showed variety expression patterns but all depends on PRAT4a completely.
  • Author(s): Yuji Motoi
  • Organizer: Innate Immunity Society(IEIIS) meeting
  • Place of Presentation: National Center of Science Building (Tokyo)
• [Presentation] Human TLR4 polymorphism D299G/T399I alerts TLR4/MD-2 conformation and response to a weak ligand monophoshoryl lipidA
  • Author(s): Natsuko Yamakawa
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] TLR4-MD-2 is negatively regulated by endogeneous ligand, glycolipid Gb4.
  • Author(s): Kondo Yuji
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Cell surface TLR1, 2 and 6 showed variety expression patterns but all depends on PRAT4a completely.
  • Author(s): Motoi Yuji
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] 脂質会合分子による免疫応答への影響
  • Author(s): 高村（赤司）祥子
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: 京都国際会館（京都）
  • Invited
• [Presentation] Human TLR4 polymorphisms influence cell surface expression and responses of TLR4
  • Author(s): Natsuko Yamakawa, Sachiko Akashi-Takamura, Umeharu Ohto, Natsuko Tanimura, Toshiyuki Shimizu and Kensuke Miyake
  • Organizer: 第４０回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] MD-1 regulates the production of anti-phospholipid antibody
  • Author(s): Sachiko Akashi-Takamura, Natsuko Yamakawa, and Kensuke Miyake
  • Organizer: 第４０回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] Intracellular TLR4/MD-2 in macrophages senses LPS and induces a
  • Author(s): Shibata T, Motoi Y, Akashi-Takamura S Tanimura N, Yamakawa N, , and Miyake K.
  • Organizer: 第４０回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] ヒトTLR4多型におけるTLR4の応答性
  • Author(s): 山川奈津子、高村（赤司）祥子、大戸梅治、谷村奈津子、清水敏之、三宅健介
  • Organizer: 感染症若手フォーラム
  • Place of Presentation: 長崎県伊王島
• [Presentation] MD-1 は抗リン脂質抗体産生を制御している
  • Author(s): 高村（赤司）祥子、山川奈津子、大戸梅治、清水敏之、三宅健介
  • Organizer: 感染症若手フォーラム
  • Place of Presentation: 長崎県伊王島
• [Remarks] 愛知医科大学 医学部 感染・免疫学講座２（旧寄生虫学）
  • URL: http://www.aichi-med-u.ac.jp/M-I2/index.html
• [Remarks] 東京大学医科学研究所感染遺伝学分野
  • URL: http://www.ims.u-tokyo.ac.jp/kanseniden/research/project04.html
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/kanseniden/index.html