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Molecular mechanisum of memory CD8 T cell differentiation

Research Project

Project/Area Number 24590573
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionChiba University

Principal Investigator

SAKAMOTO Akemi  千葉大学, 医学(系)研究科(研究院), 助教 (90359597)

Co-Investigator(Kenkyū-buntansha) TOKUHISA Takeshi  千葉大学, 学長 (20134364)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsメモリーT細胞 / CD8T細胞 / Bcl6 / 転写因子 / サイトカイン / メモリー T 細胞 / CD8 T 細胞 / CD8T細胞 / Bcl6 / 免疫記憶 / mTOR / CD4T細胞
Outline of Final Research Achievements

Bcl6, a sequence specific transcriptional repressor, is important for generation and maintenance of central memory CD8+ T cells. However, the molecular mechanism involved in the generation is largely unknown. We demonstrated that Bcl6 negatively regulates the in vivo differentiation of both activated CD25+ CD8+ T cells and KLRG1hi effector CD8+ T cells. Since the induction of CD25 expression was more rapid and the amount of phosphorylated STAT5 was higher in the in vitro activated Bcl6-deficient CD8+ T cells than in the activated wild type CD8+ T cells, the IL-2 signaling was negatively regulated in activated CD8+ T cells by Bcl6. We also confirmed the Bcl6 binding to the various regions in the CD25 and IL-2 genes. These results indicate that Bcl6 is responsible for the differentiation of memory precursor CD8+ T cells by regulating the IL-2 signaling in activated CD8+ T cells.

Report

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

    (23 results)

All 2015 2014 2013 2012 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) Book (1 results) Remarks (3 results)

  • [Journal Article] DA-Raf-dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation.2014

    • Author(s)
      Watanabe-Takano H, Takano K, Sakamoto A, Matsumoto K, Tokuhisa T, Endo T, Hatano M.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 111 Issue: 22

    • DOI

      10.1073/pnas.1321574111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells.2014

    • Author(s)
      Ikari J, Inamine A, Yamamoto T, Watanabe-Takano H, Yoshid a N, Fujimura L, Taniguchi T, Sakamoto A, Hatano M, Tatsumi K, Tokuhisa T, Arima M.
    • Journal Title

      Allergy.

      Volume: 69 Issue: 2 Pages: 223-230

    • DOI

      10.1111/all.12328

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production2013

    • Author(s)
      Okada K, Ueshima S, Kawao N, Yano M, Tamura Y, Tanaka M, Sakamoto A, Hatano M, Arima M, Miyata S, Nagai N, Tokuhisa T, and Matsuo O
    • Journal Title

      Life Sci

      Volume: 93 Issue: 2-3 Pages: 89-95

    • DOI

      10.1016/j.lfs.2013.05.023

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema.2012

    • Author(s)
      Shigeta A. et al
    • Journal Title

      Am. J. Physiol. Lung Cell Mol. Physiol.

      Volume: 303 Pages: 141-51

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV12010

    • Author(s)
      Hara K, Hashimoto H, Murakumo Y, Kobayashi S, Kogame T, Unzai S, Akashi S, Takeda S, Shimizu T, Sato M
    • Journal Title

      J Biol Chem

      Volume: 285 Issue: 40 Pages: 12299-12307

    • DOI

      10.1074/jbc.

    • Related Report
      2012 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肝臓における薬物代謝の性差を制御する新規分子の探索2015

    • Author(s)
      紙谷 聡英、近田裕美、井田絹代、坂本明美、徳久剛史.
    • Organizer
      第8回日本性差医学・医療学会学術集会
    • Place of Presentation
      ホテルクレメント徳島(徳島県・徳島市)
    • Year and Date
      2015-01-31 – 2015-02-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of enteric neurons in regulation of intestinal epithelial homeostasis.2014

    • Author(s)
      Fujimura L, Ohara Y, Arima M, Sakamoto A, Tokuhisa T, Hatano M.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府・京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肝臓における薬物代謝の性差を制御する分子メカニズム2014

    • Author(s)
      近田裕美 ら
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Possible role of enteric neurons in regulation of intestinal microbiota.2013

    • Author(s)
      Fujimura L. et al.
    • Organizer
      第42回日本免疫学会総会・学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] Bcl6 regulate production of SLAM-Associated protein in follicular helper T cells.2013

    • Author(s)
      Taniguchi T. et al.
    • Organizer
      第42回日本免疫学会総会・学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] Naive CD4 T cells are instructed to differentiate into effector or memory CD4 T cells2012

    • Author(s)
      KOHNO Mani et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] A role of Bcl6 in differentiation of memory precursor CD8 T cells2012

    • Author(s)
      PAN Jing et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際展示場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] Bcl6 is required for ICOSL expression on activated B cells2012

    • Author(s)
      IIJIMA Yuta et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulation of SLAM-associated protein in follicular helper T cells by Bcl6.2012

    • Author(s)
      Taniguchi, T. et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] Roles of ADAR1 in somatic hypermutation and class switch recombination on germinal center B cells.2012

    • Author(s)
      Turuoka, N. et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] Nitric oxide derived from enteric neurons regulates intestinal barrier function.2012

    • Author(s)
      Fujimura, L. et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      ポートピアホテル(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of IL-33 in a suppressive function of Bcl6 for IL-4 production by memory Th2 cells.2012

    • Author(s)
      Arima, M. et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際展示場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] Heterogeneity of Naive CD4 T cells

    • Author(s)
      Akemi Sakamoto et al
    • Organizer
      The 1st Symposium of International Immunological Memory and Vaccine Forum
    • Place of Presentation
      東京ステーションカンファレンス(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] Phf11 promotes IgE class switch recombination in activated B cells.

    • Author(s)
      Yamamoto T. et al
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際展示場(神戸)
    • Related Report
      2012 Research-status Report
  • [Book] Recent Res. Devel. Immunology, Roles of Bcl6 in dendritic cell homeostasis2012

    • Author(s)
      Akemi Sakamoto, Hiroyuki Matsuyama, Yuki Hayashi, Shun Hasegawa, Yuta Iijima、Mani Kohno, Jin Pan, Sumina Inage and Takeshi Tokuhisa
    • Publisher
      Research Signpost
    • Related Report
      2012 Research-status Report
  • [Remarks] 千葉大学大学院医学研究院・粘膜免疫学

    • URL

      http://www.m.chiba-u.ac.jp/class/mucosa/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 千葉大学大学院医学研究院 分化制御学

    • URL

      http://www.m.chiba-u.ac.jp/class/devgen/

    • Related Report
      2013 Research-status Report
  • [Remarks] 千葉大学 大学院医学研究院 分化制御学

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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