Exploration into MHC class II-mediated immune regulation

• Project/Area Number: 21390156
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: ISHIDO Satoshi 独立行政法人理化学研究所, 感染免疫応答研究チーム, チームリーダー (10273781)
• Co-Investigator(Kenkyū-buntansha): GOTO Eiji 独立行政法人理化学研究所, 感染免疫応答研究チーム, 研究員 (40435649)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: MHC II / ユビキチン化 / 樹状細胞 / アポトーシス / MHC class II / 遺伝子改変マウス

Research Abstract

We found that loss of MHC II ubiquitination induces Fas-mediated apoptosis of dendritic cells through the recognition by Tregs. Given that MHC II ubiquitination is promptly inhibited by several activation signals, our results suggest that loss of MHC II ubiquitination prevents excessive immune responses(i. e. autoimmunity).

Research Products

• [Journal Article] MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression (2012)
  • Author(s): Hunt, D., Wilson, JE., Weih, KA., Ishido, S., Harton, JA., Roche, PA. and Drake, JR
  • Journal Title: PLoS One Volume: 7(5) Pages: 37330-37330
  • Peer Reviewed
• [Journal Article] MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression (2012)
  • Author(s): Galbas, T., Steimle, V., Lapointe, R., Ishido, S. and Thibodeau J
  • Journal Title: Cytokine
  • Peer Reviewed
• [Journal Article] The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane (2012)
  • Author(s): Tanno, H., Yamaguchi, T., Goto, E., Ishido, S. and Komada, M
  • Journal Title: Mol. Biol. Cell Volume: 23(7) Pages: 1343-53
  • Peer Reviewed
• [Journal Article] The inter-transmembrane region of KSHV MIR2 contributes to B7-2 downregulation (2012)
  • Author(s): Kajikawa, M., Li PC., Goto, E., Miyashita, N, Aoki-Kawasumi, M, Mito-Yoshida, M, Ikegaya, M., Sugita, Y. and Ishido, S
  • Journal Title: J. Virol Volume: 86(9) Pages: 5288-96
  • Peer Reviewed
• [Journal Article] The inter-transmembrane region of KSHV MIR2 contributes to B7-2 downregulation (2012)
  • Author(s): Kajikawa, M
  • Journal Title: J.Virol. Volume: (In press)
  • Peer Reviewed
• [Journal Article] The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane (2012)
  • Author(s): Tanno, H
  • Journal Title: Mol.Biol.Cell. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Ubiquitination of CD86 Is a Key Mechanism in Regulating Antigen Presentation by Dendritic Cells (2011)
  • Author(s): Baravalle, G., Park, H., McSweeney, M., Ohmura-Hoshino, M., Matsuki, Y., Ishido, S. and Shin, JS
  • Journal Title: J. Immunol Volume: 187(6) Pages: 2966-73
  • Peer Reviewed
• [Journal Article] Anti-arthritic effect of E3 ubiquitin ligase, c-MIR, expression in the joints (2011)
  • Author(s): Toyomoto, M., Ishido, S., Miyasaka, N., Sugimoto, H. and Kohsaka, H
  • Journal Title: International immunology Volume: 23(3) Pages: 177-83
  • Peer Reviewed
• [Journal Article] CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation (2011)
  • Author(s): Tze, LE., Horikawa, K., Domaschenz, H., Howard, DR., Roots, CM., Rigby, RJ., Way, DA., Ohmura-Hoshino, M., Ishido, S., Andoniou, CE., Degli-Esposti, MA. and Goodnow, CC
  • Journal Title: J. Exp. Med Volume: 208(1) Pages: 149-65
  • Peer Reviewed
• [Journal Article] Ubiquitination of CD86 Is a Key Mechanism in Regulating Antigen Presentation by Dendritic Cells (2011)
  • Author(s): Baravalle, G
  • Journal Title: J.Immunol. Volume: 187 Pages: 2966-2973
  • Peer Reviewed
• [Journal Article] Anti-arthritic effect of E3 ubiquitin ligase, c-MIR, expression in the joints. (2011)
  • Author(s): Toyomoto, M.
  • Journal Title: International immunology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. (2011)
  • Author(s): Tze, LE.
  • Journal Title: J.Exp.Med. Volume: 208 Pages: 149-165
  • Peer Reviewed
• [Journal Article] Contribution of K11-linked ubiquitination to MIR2-mediated MHC class I internalization (2010)
  • Author(s): Goto, E., Yamanaka, Y., Ishikawa, A., Aoki-Kawasumi, M., Mito-Yoshida, M., Ohmura-Hoshino, M., Matsuki, Y., Kajikawa, M., Hirano, H. and Ishido, S
  • Journal Title: J. Biol. Chem Volume: 285(46) Pages: 35311-9
  • Peer Reviewed
• [Journal Article] Ubiquitination Regulates MHC Class II-Peptide Complex Retention and Degradation in Dendritic Cells (2010)
  • Author(s): Walseng, E., Furuta, K., Bosch, B., Weih, KA., Matsuki, Y., Bakke, O., Ishido, S. and Roche, PA
  • Journal Title: Natl. Acad. Sci Volume: 107(47) Pages: 20465-70
  • Peer Reviewed
• [Journal Article] MARCH-I : a new regulator of dendritic cell function (2010)
  • Author(s): Ishido, S., Matsuki, Y., Goto, E., Kajikawa, M. and Ohmura-Hoshino, M
  • Journal Title: Mol. Cells Volume: 29(3) Pages: 229-32
  • Peer Reviewed
• [Journal Article] Contribution of K11-linked ubiquitination to MIR2-mediated MHC class I internalization. (2010)
  • Author(s): Goto, E.
  • Journal Title: J Biol Chem. Volume: 285 Pages: 35311-35319
  • Peer Reviewed
• [Journal Article] Ubiquitination Regulates MHC Class II-Peptide Complex Retention and Degradation in Dendritic Cells. (2010)
  • Author(s): Walseng, E.
  • Journal Title: Proc.Natl.Acad.Sci.USA. Volume: 107 Pages: 20465-20470
  • Peer Reviewed
• [Journal Article] MARCH-I : A New Regulator of Dendritic Cell Function (2010)
  • Author(s): Satoshi Ishido, Yohei Matsuki, Eiji Goto, Mizuho Kajikawa, Mari Ohmura-Hoshino
  • Journal Title: Molecules and Cells 29 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Cutting edge : Requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cell (2009)
  • Author(s): Ohmura-Hoshino, M., Matsuki, Y., Mito-Yoshida, M., Goto, E., Aoki-Kawasumi, M., Nakayama, M., Ohara, O. and Ishido, S
  • Journal Title: J. Immunol Volume: 183(11) Pages: 6893-7
  • Peer Reviewed
• [Journal Article] Requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells (2009)
  • Author(s): Mari Ohmura-Hoshino, Yohei Matsuki, Mari Mito-Yoshida, Eiji Goto, Masami Aoki-Kawasumi, Manabu Nakayama, Osamu Ohara, Satoshi Ishido
  • Journal Title: THE JOURNAL OF IMMUNOLOGY 83 Pages: 6893-6897
  • Peer Reviewed
• [Presentation] ユビキチンによる膜タンパク質輸送制御とその意義について (2012)
  • Author(s): 石戸聡
  • Organizer: ATI討論会
  • Place of Presentation: 東京
  • Year and Date: 2012-03-09
• [Presentation] ユビキチン化による新たな免疫制御機構の仮説 (2011)
  • Author(s): 石戸聡
  • Organizer: 徳島大学疾患ゲノム研究センター特別セミナー
  • Place of Presentation: 徳島
  • Year and Date: 2011-12-16
• [Presentation] Inhibition of T cell differentiation by loss of MHC class II ubiquitination (2011)
  • Author(s): Rikiya ISHIKAWA
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉、幕張
  • Year and Date: 2011-11-29
• [Presentation] Requirement of MHC class II ubiquitination for survival of conventional dendritic cells in the steady state (2011)
  • Author(s): Mari Ohmura-Hoshino
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉、幕張
  • Year and Date: 2011-11-27
• [Presentation] ユビキチン化による新たな免疫制御機構 (2011)
  • Author(s): 石戸聡
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] ユビキチン化による新たな免疫制御機構Novel immune regulation by ubiquitination (2011)
  • Author(s): 石戸聡
  • Organizer: 84回日本生化学会大会
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] Molecular basis for immunoreceptor recognition by MIR2 ubiquitin ligase of KSHV (2011)
  • Author(s): 梶川瑞穂、Pai-Chi Li、後藤英治、杉田有治、石戸聡
  • Organizer: International Union of Microbiological Societies 2011 Congress(IUMS 2011)
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-15
• [Presentation] Molecular basis for immunoreceptor recognition by MIR2 ubiquitin ligase of KSHV (2011)
  • Author(s): Kajikawa Mizuho
  • Organizer: International Unions of Microbiological Societies 2011 Congress, the XV Congress of Virology
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-15
• [Presentation] MHC class IIのユビキチン化による制御 (2011)
  • Author(s): 石戸聡
  • Organizer: 神戸大学セミナー
  • Place of Presentation: 神戸
  • Year and Date: 2011-03-03
• [Presentation] A new regulator of dendritic cell function (2010)
  • Author(s): Satoshi Ishido MARCH-I
  • Organizer: INSERM-Pasteur-RCAI joint meeting Frontier in Immunology. from basic to clinics
  • Place of Presentation: 横浜
  • Year and Date: 2010-08-30
• [Presentation] MARCH-I : A new regulator of dendritic cell function (2010)
  • Author(s): Satoshi ishido
  • Organizer: INSERM-Pasteur-RCAI joint meeting
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2010-08-30
• [Presentation] Effective antigen presentation by loss of MHC class II ubiquitination (2010)
  • Author(s): Satoshi ishido
  • Organizer: 14^<TH> international congress of immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-24
• [Presentation] ユビキチン修飾系による膜タンパク質の輸送制御 (2010)
  • Author(s): 石戸聡
  • Organizer: 特定領域研究「タンパク質分解」シンポジウム「ユビキチン研究の新展開タンパク質分解・新機能・疾患」
  • Place of Presentation: 東京
  • Year and Date: 2010-08-21
• [Presentation] Novel immune regulation by ubiquitination (2009)
  • Author(s): Satoshi Ishido
  • Organizer: 32^<th> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] ユビキチンによる新たな免疫制御機構 (2009)
  • Author(s): 石戸聡
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 東京
  • Year and Date: 2009-12-10
• [Presentation] E3ユビキチンリガーゼc-MIRの抗炎症効果による関節炎治療 (2009)
  • Author(s): 豊本雅靖
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] MHC class IIのユビキチン化によるMHC class I発現の制御 (2009)
  • Author(s): 星野真理
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] カポジ肉腫関連ヘルペスウイルスMIR2による新規ポリユビキチン鎖を介したMHCclass I制御機構の解析 (2009)
  • Author(s): 後藤栄治
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] 主要組織適合抗原を制御するユビキチンリガーゼファミリー (2009)
  • Author(s): 石戸聡
  • Organizer: 第82回日本生化学大会、ワークショップ「エンドサイトーシスによる細胞機能の制御」
  • Place of Presentation: 京都
  • Year and Date: 2009-10-21
• [Presentation] 主要組織適合抗原を制御するユビキチンリガーゼファミリー (2009)
  • Author(s): 石戸聡
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Patent(Industrial Property Rights)] B7-2分子またはMHCクラスII分子等の抗原提示関連分子の細胞表面における発現を負に制御する哺乳類由来の新規タンパク質とその利用
  • Inventor(s): 石戸聡
  • Industrial Property Rights Holder: 財団法人新産業創造研究機構