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Elucidation of molecular mechanisms of the selection and maturation of thymocytes

Research Project

Project/Area Number 26293108
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Oh-hora Masatsugu  九州大学, 生体防御医学研究所, 准教授 (40351506)

Co-Investigator(Kenkyū-buntansha) 小迫 英尊  徳島大学, 藤井節朗記念医科学センター, 教授 (10291171)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
KeywordsT細胞分化 / シグナル情報伝達 / カルシウム / ヘルパーT細胞 / IL-4 / ヒストン脱メチル化 / 免疫シグナル伝達 / T細胞
Outline of Final Research Achievements

To elucidate the molecular mechanisms of the selection and maturation of thymocytes, we have analyzed the role of calcium signaling in T lymphocytes using cell-type specific Stim1 and Stim2 doubly or calcineurin b1 knockout mice. Using Foxp3-IRES-YFP/Cre Tg mice, we found that the store-operated calcium entry-calcium signaling axis is not essential for maintenance of Foxp3 expression in regulatory T cells after maturation, but is necessary for their inhibitory function. Cell maintenance of iNKT cells after maturation was normal in the absence of store-operated calcium entry. These results indicate that calcium signaling positively regulates differentiation of agonist selected thymocytes, while it positively regulates cell functions rather than cell maintenance after maturation.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (3 results)

  • [Journal Article] STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses.2017

    • Author(s)
      Yap KA, Shetty MS, Garcia-Alvarez G, Lu B., Alagappan D, Oh-hora M, Sajikumar S, Fivaz M.
    • Journal Title

      Neurobiol Learn Mem

      Volume: 138 Pages: 54-61

    • DOI

      10.1016/j.nlm.2016.08.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] C-Type Lectin Receptor MCL Facilitates Mincle Expression and Signaling through Complex Formation.2015

    • Author(s)
      Miyake Y, Masatsugu OH, Yamasaki S.
    • Journal Title

      J Immunol.

      Volume: 194 Issue: 11 Pages: 5366-74

    • DOI

      10.4049/jimmunol.1402429

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes.2015

    • Author(s)
      Garcia-Alvarez G, Shetty MS, Lu B, Yap KA, Oh-hora M, Sajikumar S, Bichler Z, Fivaz M.
    • Journal Title

      Front Behav Neurosci.

      Volume: 9

    • DOI

      10.3389/fnbeh.2015.00180

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses.2015

    • Author(s)
      Kiyotake R, Oh-Hora M, Ishikawa E, Miyamoto T, Ishibashi T, Yamasaki S.
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 42 Pages: 25322-32

    • DOI

      10.1074/jbc.m115.645234

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crossreactive αβ T cell receptors are the predominant targets of thymocyte negative selection.2015

    • Author(s)
      McDonald BD, Bunker JJ, Erickson SA, Oh-hora M, Bendelac A.
    • Journal Title

      Immunity

      Volume: 43 Issue: 5 Pages: 859-869

    • DOI

      10.1016/j.immuni.2015.09.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria.2014

    • Author(s)
      Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, Inoue H, Tanaka M, Yoneyama M, Oh-Hora M, Akashi K, Yamasaki S.
    • Journal Title

      Immunity

      Volume: 41 Issue: 3 Pages: 402-13

    • DOI

      10.1016/j.immuni.2014.08.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Stim1はマウスのエナメル質の石灰化およびエナメル芽細胞成熟期にみられる周期性を制御する2017

    • Author(s)
      古川雄亮, 春山直人, 梅田まりこ, 中西正光, 笠法子, 大洞将嗣, 呉本晃一, 吉崎恵悟, 高橋一郎
    • Organizer
      第12回九州矯正歯科学会学術大会
    • Place of Presentation
      宮崎
    • Year and Date
      2017-03-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] Loss of store-operated Ca2+ entry in T cells causes autoimmunity through follicular helper T cell activation2017

    • Author(s)
      Masatsugu Oh-hora, Xiuyuan Lu, Moe Shiokawa, Sho Yamasaki
    • Organizer
      7th International Workshop of Kyoto T cell Conference
    • Place of Presentation
      京都
    • Year and Date
      2017-03-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] STIM2 plays an essential role in IL-4 production by IL-33-timulated basophils2016

    • Author(s)
      Soichiro Yoshikawa, Masatsugu Oh-hora, Yoshinori Yamanishi, Hajime Karasuyama
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      那覇
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Loss of calcium entry in T cells causes autoimmunity associated with type 2 immune responses2016

    • Author(s)
      Masatsugu Oh-hora, Xiuyuan Lu, Moe Shiokawa, Sho Yamasaki
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] ストア作動性Ca2+流入異常による外胚葉異形成症におけるエナメル質形成不全症の発症メカニズム2016

    • Author(s)
      古川雄亮, 春山直人, 梅田まりこ, 中西正光, 笠法子, 大洞将嗣, 呉本晃一, 吉崎恵悟, 高橋一郎
    • Organizer
      第75回日本矯正歯科学会大会学術大会
    • Place of Presentation
      徳島
    • Year and Date
      2016-11-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] STIM-ORAI-mediated control of immune homeostasis2016

    • Author(s)
      Oh-hora M, Lu X, Yamasaki S.
    • Organizer
      FASEB Science Research Conference
    • Place of Presentation
      Lisbon, Portugal
    • Year and Date
      2016-06-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] カルシウム流入欠損による濾胞ヘルパーT細胞機能亢進2016

    • Author(s)
      大洞将嗣, 陸修遠, 山﨑晶
    • Organizer
      Kyoto T cell Conference
    • Place of Presentation
      京都
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] T-cell specific loss of store-operated calcium entry causes Th2-type chronic inflammation.2015

    • Author(s)
      Masatsugu Oh-hora, Xiuyuan Lu, Sho Yamasaki
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Role of STIM-mediated calcium signaling in immune system2015

    • Author(s)
      Masatsugu Oh-hora, Xiuyuan Lu, Sho Yamasaki
    • Organizer
      The 10th International Symposium of the Institute Network
    • Place of Presentation
      札幌
    • Year and Date
      2015-07-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Endoplasmic reticulum calcium sensors, Stim1 and Stim2, control dendritic cell functions.2015

    • Author(s)
      Soichiro Yoshikawa, Masatsugu Oh-hora, Kensuke Miyake, Lihua Li, Takuya Ohta, Kayo Horiguchi, Yoshinori Yamanishi, Hajime Karasuyama
    • Organizer
      NIPS International Workshop, TRPs and SOCs
    • Place of Presentation
      岡崎
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] Deficiency of Stim-dependent Ca2+ entry in T cells promotes IL-4-producing follicular helper T cell differentiation and causes chronic inflammation.2015

    • Author(s)
      大洞将嗣, 陸修遠, 山﨑晶
    • Organizer
      Kyoto T cell Conference
    • Place of Presentation
      京都
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Endoplasmic reticulum calcium sensors, Stim1 and Stim2, control dendritic cell functions.2014

    • Author(s)
      Oh-hora M, Lu X, Mori D, Yamasaki S.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Dectin-2 recognizes mycobacterial lipoarabinomannan and contributes to host defense during infection.2014

    • Author(s)
      Yonekawa A, Saijo S, Miyake Y, Ishikawa E, Suzukawa M, Yoneyama M, Oh-hora M, Yamasaki S.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular mechanism of Ca2+ influx by IgE/antigen stimulation in basophils.2014

    • Author(s)
      Yoshikawa S, Oh-hora M, Wakamori M, Miyake K, Li L, Horiguchi K, Ohta T, Adachi T, Yamanashi Y, Karasuyama H.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Calcium signaling in chronic inflammation.2014

    • Author(s)
      Oh-hora M, Lu X, Yamasaki S.
    • Organizer
      24th Hot Spring Harbor International Symposium
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-07 – 2014-11-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mechanism of chronic inflammation by the lack of store-operated calcium entry.2014

    • Author(s)
      Oh-hora M, Lu X, Yamasaki S, Takayanagi H.
    • Organizer
      FASEB Science Research Conferences
    • Place of Presentation
      Nassau, Bahamas
    • Year and Date
      2014-06-01 – 2014-06-06
    • Related Report
      2014 Annual Research Report
  • [Book] Calcium entry channels in non-excitable cells2017

    • Author(s)
      Oh-hora M, Lu X.
    • Total Pages
      19
    • Publisher
      CRC press
    • Related Report
      2016 Annual Research Report
  • [Book] Chronic Inflammation (Miyasaka M. and Takatsu K., Editors)2016

    • Author(s)
      Oh-hora M.
    • Total Pages
      14
    • Publisher
      Springer Japan
    • Related Report
      2016 Annual Research Report
  • [Book] 医学のあゆみ2014

    • Author(s)
      大洞将嗣
    • Total Pages
      2
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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