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Studies on nuclear signaling proteins required for T cell development

Research Project

Project/Area Number 25460606
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionThe University of Tokyo (2014-2015)
独立行政法人国立国際医療研究センター (2013)

Principal Investigator

Nitta Takeshi  東京大学, 医学(系)研究科(研究院), 准教授 (30373343)

Co-Investigator(Kenkyū-buntansha) OKADA Toshiyuki  国立国際医療研究センター, 研究所, 研究員 (10607328)
TAMEHIRO Norimasa  国立国際医療研究センター, 研究所, 上級研究員 (80597881)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsT細胞 / 胸腺 / TCR / シグナル伝達 / 核 / Themis / Grb2 / 免疫学 / 制御性T細胞
Outline of Final Research Achievements

Themis is a newly identified protein that localizes in cytoplasm and nucleus and is essential for inducing T cell development in the thymus. Here we found that Themis binds the adaptor protein Grb2 in the nuclei of T cells and regulates nuclear protein levels of Grb2 in T cells, and that nuclear Themis-Grb2 interaction is required for T cell development. However, the nuclear localization of Themis is dispensable for cytokine production by peripheral T cells, suggesting that Themis has different functions in the thymus and periphery. Our results also show that two CABIT domains in Themis are both required for T cell development and that each of the CABIT domains exerts distinct functions during T cell development.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (26 results)

All 2016 2015 2014 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 1 results,  Open Access: 3 results) Presentation (15 results) (of which Invited: 3 results) Remarks (3 results)

  • [Journal Article] Thymic stromal cell subsets for T cell development.2016

    • Author(s)
      Nitta T, Suzuki H
    • Journal Title

      Cellular and Molecular Life Science

      Volume: 73 Issue: 5 Pages: 1021-1037

    • DOI

      10.1007/s00018-015-2107-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] IL-17-producing γδ T cells enhance bone regeneration2016

    • Author(s)
      Ono T, et al.
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 10928-10928

    • DOI

      10.1038/ncomms10928

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fezf2 orchestrates the thymic program of self-antigen expression for immune tolerance.2015

    • Author(s)
      Takaba H, Morishita Y, Tomofuji Y, Danks L, Nitta T, Komatsu N, Kodama T, Takayanagi H
    • Journal Title

      Cell

      Volume: 163 Issue: 4 Pages: 975-987

    • DOI

      10.1016/j.cell.2015.10.013

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] LXR Agonism Upregulates the Macrophage ABCA1/Syntrophin Protein Complex That Can Bind ApoA-I and Stabilized ABCA1 Protein, but Complex Loss Does Not Inhibit Lipid Efflux.2015

    • Author(s)
      Tamehiro N, Park MH, Hawxhurst V, Nagpal K, Adams ME, Zannis VI, Golenbock DT, Fitzgerald ML
    • Journal Title

      Biochemistry

      Volume: 54 Issue: 46 Pages: 6931-6941

    • DOI

      10.1021/acs.biochem.5b00894

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint.2015

    • Author(s)
      Tamehiro N, Oda H, Shirai M, Suzuki H.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 6 Pages: e0131047-e0131047

    • DOI

      10.1371/journal.pone.0131047

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The thymic cortical epithelium determines the TCR repertoire of IL-17-producing gdT cells.2015

    • Author(s)
      Nitta T, Muro R, Shimizu Y, Nitta S, Oda H, Ohte Y, Goto M, Yanobu R, Narita T, Takayanagi H, Yasuda H, Okamura T, Murata T, Suzuki H.
    • Journal Title

      EMBO Rep.

      Volume: なし Issue: 5 Pages: 638-653

    • DOI

      10.15252/embr.201540096

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Ras GTPase-activating protein Rasal3 supports survival of naïve T cells.2015

    • Author(s)
      Muro R, Nitta T, Okada T, Ideta H, Tsubata T, Suzuki H
    • Journal Title

      PLoS One

      Volume: 10 Issue: 3 Pages: e0119898-e0119898

    • DOI

      10.1371/journal.pone.0119898

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Function of Themis CABIT Domains during T Cell Development.2014

    • Author(s)
      Okada T, Nitta T, Kaji K, Takashima A, Oda H, Tamehiro N, Goto M, Okamura T, Patrick MS, Suzuki H.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 2 Pages: e89115-e89115

    • DOI

      10.1371/journal.pone.0089115

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] RhoH is essential for development of IL-17-producing γδ T cells2015

    • Author(s)
      Ryunosuke Muro, Takeshi Nitta, Norimasa Tamehiro, Hiroyo Oda, Harumi Suzuki
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Differential roles of TCR-proximal signaling adaptors in T cell development2015

    • Author(s)
      Harumi Suzuki, Norimasa Tamehiro, Ryunosuke Muro, Hiroyo Oda, Takeshi Nitta, Akihiro Kimura
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] γδT細胞の分化を制御する胸腺環境因子の解析2015

    • Author(s)
      成田知也、室龍之介、鈴木春巳、高柳 広、新田 剛
    • Organizer
      Kyoto T cell Conference
    • Place of Presentation
      京都市
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 胸腺皮質上皮細胞の欠損を示すbeta5t変異マウスの発見2015

    • Author(s)
      新田 剛、室龍之介、鈴木春巳
    • Organizer
      第34回日本胸腺研究会
    • Place of Presentation
      相模原市
    • Year and Date
      2015-02-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Themis is important for differentiation of regulatory T cells2014

    • Author(s)
      Toshiyuki Okada, Takeshi Nitta, Masayuki Kitajima, Hiroyo Oda, Harumi Suzuki
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Thymic cortical epithelium controls development of IL-17-producing γδT cells2014

    • Author(s)
      Takeshi Nitta, Ryunosuke Muro, Hiroshi Takayanagi, Harumi Suzuki
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Over expression of RhoH activates the transition of CD4-CD8-(DN) to CD4+CD8+ (DP) cells in RAG-/- background.2014

    • Author(s)
      Norimasa Tamehiro, Hiroyo Oda, and Harumi Suzuki
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] 免疫システムを形づくる胸腺微小環境2014

    • Author(s)
      新田 剛
    • Organizer
      第5回関東甲越免疫不全症研究会
    • Place of Presentation
      東京都
    • Year and Date
      2014-09-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 胸腺微小環境の新機能2014

    • Author(s)
      新田 剛
    • Organizer
      沖縄感染免疫シンポジウム2014
    • Place of Presentation
      那覇市
    • Year and Date
      2014-07-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 胸腺皮質上皮細胞によるγδT細胞の分化制御2014

    • Author(s)
      新田 剛、室 龍之介、新田 幸子、小田 浩代、鈴木 春巳
    • Organizer
      第24回 Kyoto T Cell Conference
    • Place of Presentation
      京都市
    • Year and Date
      2014-05-16 – 2015-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] RhoH欠損マウスで認められる乾癬様皮膚炎の解析2014

    • Author(s)
      為広紀正、小田浩代、鈴木春巳
    • Organizer
      第24回 Kyoto T Cell Conference
    • Place of Presentation
      京都市
    • Year and Date
      2014-05-16 – 2014-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] CRISPR/Casシステムを利用したナイーブT細胞減少(TN)マウスの原因遺伝子の同定2014

    • Author(s)
      岡村匡史、高梨理絵子、後藤元人、清水有紀子、鈴木春巳、新田 剛
    • Organizer
      第61回日本実験動物学会総会
    • Place of Presentation
      札幌市
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Thymic cortical epithelium determines the TCR repertoire of IL-17-producing γδT cells2014

    • Author(s)
      Takeshi Nitta, Ryunosuke Muro, Sachiko Nitta, Hiroyo Oda, Harumi Suzuki
    • Organizer
      ThymOz International Conference
    • Place of Presentation
      Heron Island, Queensland, Australia
    • Year and Date
      2014-04-02 – 2014-04-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Themis regulates cytokine production in mature naïve T cells2014

    • Author(s)
      Toshiyuki Okada, Takeshi Nitta, Norimasa Tamehiro, Patrick Michael, Harumi Suzuki
    • Organizer
      ThymOz International Conference
    • Place of Presentation
      Heron Island, Queensland, Australia
    • Year and Date
      2014-04-02 – 2014-04-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Differential function of two CABIT domains in Themis

    • Author(s)
      Toshiyuki Okada, Takeshi Nitta, Hiroyo Oda, Michael Scott Patrick, Harumi Suzuki
    • Organizer
      日本免疫学会総会・学術集会 2013
    • Place of Presentation
      千葉市
    • Related Report
      2013 Research-status Report
  • [Remarks] 東京大学大学院医学系研究科 免疫学

    • URL

      http://www.osteoimmunology.com/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 国立国際医療研究センター 免疫病理研究部

    • URL

      http://plaza.umin.ac.jp/~suzukih/cgi-bin/lab/index.cgi

    • Related Report
      2015 Annual Research Report
  • [Remarks] 国立国際医療研究センター研究所 免疫病理研究部

    • URL

      http://plaza.umin.ac.jp/~suzukih/cgi-bin/lab/index.cgi

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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