The roles of novel MHC receptors, MMRs, in molecular mechanism of allograft rejection

• Project/Area Number: 23791505
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Kansai University of Welfare Sciences (2014-2015); Osaka Medical College (2011-2013)
• Principal Investigator: Tashiro-Yamaji Junko 関西福祉科学大学, 健康福祉学部, 准教授 (40340559)
• Research Collaborator: Yamana Hidenori 大阪医科大学, 消化器外科学, 大学院生 ; Maeda Shogo 大阪医科大学, 形成外科学, 大学院生
• Project Period (FY): 2011-04-28 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 移植免疫 / 同種異系移植 / 自然免疫 / 移植・再生医療 / 免疫学 / 遺伝子 / 細胞・組織 / 生体分子

Outline of Final Research Achievements

Recently, we have isolated two novel receptors for allogeneic MHCs on macrophages/monocytes, Macrophage MHC receptor1 (MMR1) and MMR 2. In this study, we examined the physiological roles of MMR1 and MMR2. Study using generation of MMR2 knockout (KO) mice on a C57BL/6 background or binding assay with MHC molecules demonstrated that MMR1 and 2 were bound to 1 to 3 allogeneic MHC class I molecules and that MMR1 and 2 on monocytes/macrophages in mice were essential for recognition and rejection of allografted skin.

Research Products

• [Journal Article] Blood supply-susceptible formation of melanin pigment in hair bulb melanocytes of mice. (2015)
  • Author(s): Maeda S, Ueda K, Yamana H, Tashiro-Yamaji J, Ibata M, Mikura A, Okada M, Yasuda E, Shibayama Y, Yoshino M, Kubota T, Yoshida R.
  • Journal Title: Plast Reconstr Surg Glob Open Volume: e328 Issue: 3 Pages: 1-9
  • DOI: 10.1097/gox.0000000000000284
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Down-regulated expression of monocyte/macrophage major histocompatibility complex receptors in human and mouse monocytes by expression of their ligands. (2014)
  • Author(s): Yamana H, Tashiro-Yamaji J, Hayashi M, Maeda S, Shimizu T, Tanigawa N, Uchiyama K, Kubota T, Yoshida R.
  • Journal Title: Clin Exp Immunol. Volume: 178 Issue: 1 Pages: 118-128
  • DOI: 10.1111/cei.12383
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Macrophage MHC and T-cell receptors essential for rejection of allografted skin and lymphoma. (2013)
  • Author(s): Tashiro-Yamaji J, Maeda S, Ikawa M, Okabe M, Kubota T, and Yoshida R
  • Journal Title: Transplantation Volume: 96 (3) Issue: 3 Pages: 251-257
  • DOI: 10.1097/tp.0b013e3182985527
  • Peer Reviewed
• [Journal Article] Specific binding of HLA-B44 to human macrophage MHC receptor 1 on monocytes. (2012)
  • Author(s): Tashiro-Yamaji J, Shimizu T, Hayashi M, Yamana H, Tanigawa N, Uchiyama K, Kubota T, Yoshida R.
  • Journal Title: Gene Volume: 501 (2) Pages: 127-34
  • Peer Reviewed
• [Journal Article] Transgene Number-dependent, Gene Expression Rate-independent Rejection of Dd-, Kd-, or DdKd-Transgened Mouse Skin or Tumor Cells from C57BL/6 (DbKb) Mice. (2011)
  • Author(s): Inoue Y, Tashiro-Yamaji J, Hayashi M, Kiyonari H, Shimizu T, Ibata M, Yamana H, Kubota T, Tanigawa N, Yoshida R.
  • Journal Title: Microbiology and Immunology Volume: 55 Issue: 6 Pages: 446-453
  • DOI: 10.1111/j.1348-0421.2011.00337.x
  • NAID: 10031121489
  • Peer Reviewed
• [Journal Article] Isolation and characterization of a cDNA encoding a novel human receptor homologous to mouse macrophage major histocompatibility complex (MHC) receptor(MMR)1 (2011)
  • Author(s): Junko Tashiro-Yamaji, Tetsunosuke Shimizu, Hidenori Yamana, Wakako Miyachi, Keiko Hasegawa, Yukako Shiraiwa, Yoshiaki Mori, Ryotaro Yoshida, and Takahiro Kubota.
  • Journal Title: J Physiological Sciences Volume: 61(1)
• [Presentation] Role of unsaturated fatty acids on expression of myosin heavy chain type II b mRNA in mouse myocytes. (2016)
  • Author(s): Junko Yamaji et al.
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 北海道、札幌市
  • Year and Date: 2016-03-22
• [Presentation] Enhancement of myosin heavy chain class I (MHC I) mRNA expression in C2C12 myocyte by multivalent cations (2015)
  • Author(s): Mori Y., Yamaji J., Hiroshima R., et al.
  • Organizer: 第120回日本解剖学会総会全国学術大会・第92回日本生理学会大会合同大会
  • Place of Presentation: 神戸コンベンションセンター(神戸国際会議場・神戸国際展示場)（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Enhancement of myosin heavy chain class I (MyHC I) mRNA expression in C2C12 myocyte by chlorogenic acid (2014)
  • Author(s): Yamaji J., et al.
  • Organizer: WMS2014
  • Place of Presentation: Thaersaal, Humboldt university（Berlin）
  • Year and Date: 2014-10-08
• [Presentation] Essential role of Macrophage MHC receptor (MMR) in allograft rejection: generation and analysis of MMR2 knockout mice (2014)
  • Author(s): Tashiro-Yamaji J, Maeda S, Ikawa M, Okabe M, Daikoku E, Saito M, Shiraiwa Y, Yoshida R, and Kubota T.
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島県鹿児島市 鹿児島大学郡元キャンパス
• [Presentation] The role of Macrophage MHC receptor (MMR)1 in allorecognition: Isolation of a cDNA encoding a novel MHC receptor for HLA-B44, human MMR1 (2013)
  • Author(s): Tashiro-Yamaji J, Shimizu T, Daikoku E, Saito M, Shiraiwa Y, Yoshida R, and Kubota T.
  • Organizer: 37th Congress of the International Union of Physiological Sciences (IUPS2013)
  • Place of Presentation: イギリス、バーミンガム
• [Presentation] Establishment and analysis of MMR2 knockout mice: the role of Macrophage MHC receptor (MMR) 1 and 2 in allograft rejection (2013)
  • Author(s): Junko Tashiro-Yamaji, Shogo Maeda, Masahito Ikawa, Masaru Okabe, Hidenori Yamana, Natsuki Hannya, Masahisa Saito, Eriko Daikoku, Yuka Shiraiwa, Ryotaro Yoshida, and Takahiro Kubota.
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京都江戸川区
• [Presentation] ヒト単球/マクロファージMHC受容体（MMR）によるHLAの識別 (2012)
  • Author(s): 山路-田代純子、清水徹之介、山名秀典、前田尚吾、般若夏樹、窪田隆裕、吉田龍太郎
  • Organizer: 第23回日本生体防御学会学術総会
  • Place of Presentation: 東京都・品川区
• [Presentation] The roles of Monocyte/Macrophage MHC receptors (MMRs) in allograft rejection: the generation of MMR2 deficient mice (2012)
  • Author(s): TASHIRO-YAMAJI Junko, MAEDA Shogo, IKAWA Masahito, OKABE Masaru, INOUE Yoshihiro, SHIMIZU Tetsunosuke, YAMANA Hidenori, HANNYA Natsuki, KUBOTA Takahiro, YOSHIDA Ryotaro.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 兵庫県・神戸市
• [Presentation] Specific binding of HLA-A32, -B13 and -B62 molecules to human monocyte/macrophage MHC receptor 2 on monocytes (2012)
  • Author(s): YAMANA Hidenori, TASHIRO-YAMAJI Junko, SHIMIZU Tetsunosuke, HAYASHI Michihiro, TANIGAWA Nobuhiko, UCHIYAMA Kazuhisa, KUBOTA Takahiro, YOSHIDA Ryotaro.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 兵庫県・神戸市
• [Presentation] Isolation of a human cDNA homologous to a mouse cDNA encoding a receptor for allogeneic MHC (H-2Dd) [macrophage MHC receptor 1 (MMR1)] (2012)
  • Author(s): Junko Tashiro-Yamaji, Tetsunosuke Shimizu, Hidenori Yamana, Shogo Maeda, Natsuki Hannnya, Masahisa Saito, Eriko Daikoku, Yuka Shiraiwa, Ryotaro Yoshida, and Takahiro Kubota.
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本市・信州大 松本キャンパス、松本市文化会館、松本市総合体育館
• [Presentation] マウスマクロファージMHC受容体（MMR）1・2 の非自己（同種異系）識別機構の解析 (2011)
  • Author(s): 山路 純子（田代 純子）、清水徹之介、山名秀典、前田尚吾、般若夏樹、大黒恵理子、齊藤昌久、森 禎章、白岩有桂、吉田龍太郎、窪田隆裕
  • Organizer: 日本生理学会 第104回近畿生理談話会
  • Place of Presentation: 大阪医科大学
• [Presentation] Characterization of a novel human receptor homologous to mouse macrophage major histocompatibility complex (MHC) receptor(MMR)1 (2011)
  • Author(s): Junko Tashiro-Yamaji, Tetsunosuke Shimizu, Hidenori Yamana, Shogo Maeda, Natsuki Hannya, Takahiro Kubota, and Ryotaro Yoshida.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉市・幕張メッセ
• [Remarks] J Physiological Sciences誌による研究発表は、東北大震災の影響により、J Physiological Sciences誌上開催に切り替えられた第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会合同大会（予定開催地：横浜市・パシフィコ横浜）における研究内容を示す。