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The role of the transcription factor Tox2 in Treg and Tfh biology

Research Project

Project/Area Number 18K07175
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionOsaka University

Principal Investigator

Wing James  大阪大学, 感染症総合教育研究拠点, 准教授 (00648694)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsRegulatory T-cells / T-follicular helper / T-follicular regulatory / Antibodies / Germinal center / Mass cytometry (CyTOF) / Mass Cytometry (CyTOF) / Mass Cytometry / Regulatory T-cell (Treg) / Tfollicular reg (Tfr) / Tfollicular helper (Tfh) / CyTOF / Treg / Tfh / Tfr / B-cell
Outline of Final Research Achievements

We explored the role of the Tox2 gene in the biology of regulatory T-cells (Treg) and T-follicular regulatory cells (Tfr), that are critical to control of antibodies. Using a Treg specific Tox2 knockout system we found that loss of Tox2 in Tregs caused a functional defect and an increased number of T-cells that help antibody production (Tfh) and germinal center B-cells, the type of B-cell that produces high quality antibodies. Additionally we found increased levels of IgA antibody that is important to control of immunity at the mucosal sites such as the gut. We also overexpressed the Tox2 gene in conventional T-cells and Tregs which confirmed its function to increase genes important to control antibody regulation. Taken together, our results demonstrate for the first time that Tox2 plays an important role in regulatory cells after immune challenge.

Academic Significance and Societal Importance of the Research Achievements

This study found new information regarding the control of regulatory T-cells. Since these cells are responsible for the control of vaccine responses and autoimmunity we believe that these results may allow us to control these cells and lead to the production of improved vaccines and medicines.

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (24 results)

All 2021 2020 2019 2018 Other

All Journal Article (12 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Using Mass Cytometry to Address Tfh and Tfr Heterogeneity2021

    • Author(s)
      Wing James B.、Sakaguchi Shimon
    • Journal Title

      Methods in Molecular biology

      Volume: - Pages: 47-57

    • DOI

      10.1007/978-1-0716-1736-6_5

    • ISBN
      9781071617359, 9781071617366
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Isolation and Characterization of Both Human and Mouse Tfh/Tfr Cells2021

    • Author(s)
      Tulyeu Janyerkye、Sondergaard Jonas N.、Sakaguchi Shimon、Wing James B.
    • Journal Title

      Current Protocols

      Volume: 1 Issue: 11

    • DOI

      10.1002/cpz1.283

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CTLA-4 expression by B-1a B cells is essential for immune tolerance2021

    • Author(s)
      Yang Yang、Li Xiao、Ma Zhihai、Wang Chunlin、Yang Qunying et al
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 525-525

    • DOI

      10.1038/s41467-020-20874-x

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Control of foreign Ag‐specific Ab responses by Treg and Tfr2020

    • Author(s)
      Wing James B.Lim Ee Lyn、Sakaguchi Shimon
    • Journal Title

      Immunological Reviews

      Volume: 296 Issue: 1 Pages: 104-119

    • DOI

      10.1111/imr.12888

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamics of effector and naive Regulatory T cells throughout pregnancy2020

    • Author(s)
      Shigeta Naoya、Kumasawa Keiichi、Tanaka Atsushi、Badger Wing James、Nakamura Hitomi、Sakaguchi Shimon、Kimura Tadashi
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 140 Pages: 103135-103135

    • DOI

      10.1016/j.jri.2020.103135

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory T Cells and Human Disease2020

    • Author(s)
      Sakaguchi Shimon、Mikami Norihisa、Wing James B.、Tanaka Atsushi、Ichiyama Kenji、Ohkura Naganari
    • Journal Title

      Annual Review of Immunology

      Volume: 38 Issue: 1 Pages: 541-566

    • DOI

      10.1146/annurev-immunol-042718-041717

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Control of Regulatory T Cells by Co-signal Molecules2019

    • Author(s)
      Wing James Badger、Tay Christopher、Sakaguchi Shimon
    • Journal Title

      Co-signal Molecules in T Cell Activation

      Volume: 1189 Pages: 179-210

    • DOI

      10.1007/978-981-32-9717-3_7

    • ISBN
      9789813297166, 9789813297173
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)2019

    • Author(s)
      Cossarizza A,…150 authors…,Wing, JB….16 authors… Zychlinsky A
    • Journal Title

      European Journal of Immunology

      Volume: 49 Issue: 10 Pages: 1457-1973

    • DOI

      10.1002/eji.201970107

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer2019

    • Author(s)
      Wing James B.、Tanaka Atsushi、Sakaguchi Shimon
    • Journal Title

      Immunity

      Volume: 50 Issue: 2 Pages: 302-316

    • DOI

      10.1016/j.immuni.2019.01.020

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 濾胞性制御性T細胞2019

    • Author(s)
      木本 富子, Wing James B.
    • Journal Title

      Journal of Clinical and Experimental Medicine (Igaku No Ayumi)

      Volume: 268 Pages: 1106-1110

    • Related Report
      2018 Research-status Report
  • [Journal Article] Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody2018

    • Author(s)
      Ha Danbee、Tanaka Atsushi、Kibayashi Tatsuya、Tanemura Atsushi、Sugiyama Daisuke、Wing James Badger、Lim Ee Lyn、Teng Karen Wei Weng、Adeegbe Dennis、Newell Evan W.、Katayama Ichiro、Nishikawa Hiroyoshi、Sakaguchi Shimon
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 2 Pages: 609-618

    • DOI

      10.1073/pnas.1812186116

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Control of Germinal Center Responses by T-Follicular Regulatory Cells2018

    • Author(s)
      Wing James B.、Tekguc Murat、Sakaguchi Shimon
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 1910-1917

    • DOI

      10.3389/fimmu.2018.01910

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Using mass cytometry to uniderstand human immunity to infectious disease2021

    • Author(s)
      James B Wing
    • Organizer
      25th annual meeting of the Japanese society for immunology
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] High dimensional analysis of T-follicular regulatory cells2020

    • Author(s)
      James Wing
    • Organizer
      IMSUT young investigators symposium “Rising stars in cutting edge Immunology research”
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Exploring regulatory T cell function and phenotype with mass cytometry2019

    • Author(s)
      James Wing
    • Organizer
      2019 Japanese society for Immunology, lunch time technical seminar
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] High dimensional analysis of T-follicular regulatory cells2019

    • Author(s)
      James Wing
    • Organizer
      2019 Japanese society for Immunology
    • Related Report
      2019 Research-status Report
  • [Presentation] Exploring regulatory T cell function and phenotype with mass cytometry2019

    • Author(s)
      James Wing
    • Organizer
      8th Annual Fluidigm Mass Cytometry Summit
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] High dimensional analysis of T-follicular regulatory cells2019

    • Author(s)
      Wing James B.
    • Organizer
      B Cell-T cell interactions, Keystone Symposium, Colorado, USA
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] T-follicular regulatory cells in mice and humans2018

    • Author(s)
      Wing James B.
    • Organizer
      Invited lecture at National cancer center, Chiba.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] T-follicular regulatory cells in mice and humans2018

    • Author(s)
      Wing James B.
    • Organizer
      Invited lecture at Nagoya city university, Nagoya.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Exploring regulatory T-cell phenotype and function in mice and humans with CyTOF2018

    • Author(s)
      Wing James B.
    • Organizer
      第1回 Japan CyTOF User meeting, Tokyo.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] T-follicular regulatory cells in human blood2018

    • Author(s)
      Wing James B.
    • Organizer
      47th Annual meeting of the Japanese society for Immunology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] Clinical Immunology: Principles and practice. Fifth Edition. Chapter: Regulatory Immune cells.2018

    • Author(s)
      Wing, James Badger. Shimon Sakaguchi.
    • Total Pages
      1319
    • Publisher
      Elsevier
    • ISBN
      9780702068966
    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      http://www.ifrec.osaka-u.ac.jp/jpn/laboratory/wing_james_badger/

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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