Immunological Abnormality caused by MARCH I/c-MIR 2 deficiency

• Project/Area Number: 21590422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HOSHINO Mari 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 (10313511)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: E3ユビキチンリガーゼ / 樹状細胞

Research Abstract

We have investigated the physiological function of MARCH(membrane associated RING-CH protein) family. So far, we reported that MARCH-I-deficient cDCs and B cells accumulated MHC II and B7-2 and exhibited low Ag-presenting ability for exogenous Ags. Furthermore, MHC II, but not B7-2, was required for impaired cDC function induced by loss of MARCH-I in vivo. On this study we found that conditional inhibition of MARCH-I induced natural Treg-dependent apoptosis of mature DCs due to loss of MHC II ubiquitination. Our results suggest that maturation of DCs induces their "suicide" by facilitating recognition by Tregs, which is induced by loss of pMHC II ubiquitination in the steady state.

Research Products

• [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, Shin JS.
  • Journal Title: J Immunol Volume: 187(6) Pages: 2966-73
  • 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, Goodnow CC.
  • Journal Title: J Exp Med Volume: 208 Pages: 149-165
  • Peer Reviewed
• [Journal Article] MARCH-I : A new regulator of dendritic cell function (2010)
  • Author(s): Ishido S, Matsuki Y, Goto E, Kajikawa M, Ohmura-Hoshino M.
  • Journal Title: Mol Cells
• [Journal Article] Cutting edge : requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells (2009)
  • Author(s): Ohmura-Hoshino M, Matsuki Y, Mito-Yoshida M, Goto E, Aoki-Kawasumi M, Nakayama M, Ohara O, Ishido S.
  • Journal Title: J Immunol Volume: 183(11) Pages: 6893-7
  • Peer Reviewed
• [Presentation] MHCクラスIIのユビキチン化は樹状細胞の維持に重要である (2011)
  • Author(s): 星野真理,松木洋平、水戸麻理、石川力也、後藤栄治、梶川瑞穂、八木田秀雄、石戸聡
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉、幕張メッセ
  • Year and Date: 2011-11-27
• [Presentation] Effective antigen presentation by loss of MHC class II ubiquitination (2010)
  • Author(s): 松木洋平,星野真理、後藤栄治、梶川瑞穂、石戸聡
  • Organizer: 14^<th> International congress of Immunology
  • Place of Presentation: 神戸
• [Presentation] MARCH Iによる樹状細胞の制御 (2009)
  • Author(s): 星野真理、松木洋平、水戸麻理、青木雅美、後藤栄治、石戸聡
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪国際会議場、大阪