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Novel immune regulation through regulated MHC II ubiquitination

Research Project

Project/Area Number 24390122
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Immunology
Research InstitutionShowa Pharmaceutical University

Principal Investigator

ISHIDO Satoshi  昭和薬科大学, 薬学部, 教授 (10273781)

Co-Investigator(Renkei-kenkyūsha) NAOE Yoshinori  独立行政法人国立長寿医療センター, 老化機構研究部免疫研究室, 室長 (50392048)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywordsユビキチン / MHC class II / 樹状細胞 / 抗原提示 / CD86 / 寛容 / IgE
Outline of Final Research Achievements

pMHC II are continuously replaced with newly generated pMHC II through continuous ubiquitination by MARCH-I. The recycling of pMHC II is thought to be necessary for quick immune response against newly invading pathogens. In contrast, infectious stimuli inhibit recycling of pMHC II through inhibition of MARCH-I-mediated ubiquitination,thereby initiating immunity. Therefore, we are challenging to have experimental evidence for the hypotheses. We have generated the mice whose pMHC II is continuously ubiquitinated. This mouse showed impairment of immune response. In addition, the number of lymphocyte was reduced in the periphery. In MHC II-deficient mice, the number of leukocyte including lymphocyte was increased in the periphery, indicating that reduction of lymphocyte number is not simply due to down-regulation of MHC II in this mouse. Our results support the present hypothesis and suggest that regulated ubiquitination of pMHC II requires homeostasis of lymphocytes.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (12 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (5 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells2014

    • Author(s)
      Ishikawa, R., Kajikawa, M., and Ishido, S.
    • Journal Title

      Int. Immunol.

      Volume: 未定 Issue: 5 Pages: 283-289

    • DOI

      10.1093/intimm/dxt066

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2.2013

    • Author(s)
      Sugiura, A., Nagashima, S., Tokuyama, T., Amo, T., Matsuki, Y., Ishido, S., Kudo, Y., McBride, H.M., Fukuda, T., Matsushita, T., Inatome, R., and C Yanagi, S.
    • Journal Title

      Mol. Cell

      Volume: 51 Issue: 1 Pages: 1-15

    • DOI

      10.1016/j.molcel.2013.04.023

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cells.2013

    • Author(s)
      Oh J, Wu N, Baravalle G, Cohn B, Ma J, Lo B, Mellman I, Ishido S, Anderson M, Shin JS.
    • Journal Title

      J Exp Med.

      Volume: 210 Issue: 6 Pages: 1069-1077

    • DOI

      10.1084/jem.20122695

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Encounter with antigen-specific promed CD4 cells promotes MHC class II degradation in dendritic cells.2012

    • Author(s)
      Furuta, K.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 109 Issue: 47 Pages: 19380-19385

    • DOI

      10.1073/pnas.1213868109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Ankrd 13 family of UIM -bearing proteins regulates EGF receptor end ocytosis from the plasma membrane.2012

    • Author(s)
      Tanno, H.
    • Journal Title

      Mol. Biol. Cell.

      Volume: 59 Pages: 1343-1353

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Loss of MHC II ubiquitination induces negative consequence to dendritic cells2014

    • Author(s)
      satoshi ishido
    • Organizer
      8th International Workshop on Antigen Processing & Presentation
    • Place of Presentation
      The Academy of Natural Sciences of Drexel University, Philadelphia, US
    • Year and Date
      2014-06-10 – 2014-06-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Loss of MHC class II ubiquitination negatively regulates dendritic cells.2013

    • Author(s)
      Satoshi Ishido
    • Organizer
      THE 35th NAITO CONFERENCE
    • Place of Presentation
      Chateraise Gateaux Kingdom (札幌)
    • Related Report
      2013 Annual Research Report
  • [Presentation] High antigen-specific IgE production in MARCH8 transgenic mice2012

    • Author(s)
      星野真理
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2012-12-06
    • Related Report
      2012 Annual Research Report
  • [Presentation] Regulation of CD4 T cell development by MARCH-I2012

    • Author(s)
      石川力也
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2012-12-06
    • Related Report
      2012 Annual Research Report
  • [Presentation] KSHV免疫回避分子MIRによる免疫受容体の認識機構2012

    • Author(s)
      梶川瑞穂
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2012-11-13
    • Related Report
      2012 Annual Research Report
  • [Remarks] 昭和薬科大学 統合感染免疫学研究室

    • URL

      http://www.shoyaku.ac.jp/labosite/kansen/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 昭和薬科大学統合感染免疫学研究室

    • URL

      http://www.shoyaku.ac.jp/labosite/kansen/index.html

    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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