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Molecular mechanisms of T cell development and functional differentiation in the thymus

Research Project

Project/Area Number 15K08524
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KIMURA Motoko  千葉大学, 大学院医学研究院, 准教授 (00345018)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords免疫学 / 胸腺 / 胸腺内細胞分化 / 細胞の運命決定 / T細胞 / ヘルパー機能 / TCRシグナル / Thpok / Runx3 / 細胞運命決定 / 胸腺内分化
Outline of Final Research Achievements

Functional lineage-decision either becoming helper lineage cells or killer lineage cells is determined by the duration of TCR signaling that developing T cells receive. Long duration of TCR signaling promotes helper lineage (i.e. CD4T cells); whereas short duration of TCR signaling results in the development of killer cells (i.e. CD8T cells). In this study, we have found that helper function is imposed by TCR signaling independently of Thpok expression so that all positively selected developing cells including MHC-I selected cells once acquire the helper function. However, during CD8T cell development, cytokine-induced Runx3d expression suppresses helper function and endows killer function. In summary, our data reveal that "functional reversal" is occurred during CD8T cell development.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Remarks (2 results)

  • [Int'l Joint Research] 国立衛生研究所 国立がん研究所 (NCI/ NIH)(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Crucial role for CD69 in allergic inflammatory responses: CD69-Myl9 system in the pathogenesis of airway inflammation2017

    • Author(s)
      Kimura Motoko Y.、Hayashizaki Koji、Tokoyoda Koji、Takamura Shiki、Motohashi Shinichiro、Nakayama Toshinori
    • Journal Title

      Immunol. Rev.

      Volume: 278 Issue: 1 Pages: 87-100

    • DOI

      10.1111/imr.12559

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Timing and duration of MHC I positive selection signals are adjusted in the thymus to prevent lineage errors2016

    • Author(s)
      Kimura, M. Y., Thomas, J., Tai, X., Guinter, T. I., Shinzawa, M., Etzenperger, R., Li, Z., Love, P., Nakayama, T., and Singer, A.
    • Journal Title

      Nat. Immunol.

      Volume: 17 Issue: 12 Pages: 1415-1423

    • DOI

      10.1038/ni.3560

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Myosin light chain 9 and 12 are functional ligands for CD69 that regulate airway inflammation2016

    • Author(s)
      Hayashizaki, K., Kimura, M. Y., Tokoyoda, K., Hosokawa, H., Shinoda, K., Hirahara, K., Ichikawa, T., Onodera, A., Hanazawa, A., Iwamura, C., Kakuta, J., Muramoto, K., Motohashi, S., Tumes, D. J., Iinuma, T., Yamamoto, H., Ikehara, Y., Okamoto, Y., and Nakayama, T.
    • Journal Title

      Sci. Immunol.

      Volume: 1 Issue: 3

    • DOI

      10.1126/sciimmunol.aaf9154

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Methylation of Gata3 at Arg261 regulates transactivation of the Il5 gene in T helper 2 cells2015

    • Author(s)
      Hosokawa, H., Kato, M., Tohyama, H., Tamaki, Y., Endo, Y., Kimura, M. Y., Tumes, D. J., Motohashi, S., Matsumoto, M., Nakayama, K. I., Tanaka, T., and Nakayama, T.
    • Journal Title

      J Biol Chem

      Volume: in press Issue: 21 Pages: 13095-13103

    • DOI

      10.1074/jbc.m114.621524

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Let-7 microRNAs target the lineage-specific transcription factor PLZF to regulate terminal NKT cell differentiation and effector function2015

    • Author(s)
      Pobezinsky, L.A., Etzensperger, R., Jeurling, S., Alag, A., Kadakia, T., McCaughtry, T.M., Kimura, M.Y., Sharrow, S.O., Guinter, T.I., Feigenbaum, L. and Singer, A.
    • Journal Title

      Nature Immunology

      Volume: 16 Issue: 5 Pages: 517-524

    • DOI

      10.1038/ni.3146

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] CD69-Myl9 system regulates pathogenesis of inflammatory disorders2018

    • Author(s)
      Kimura M.Y., Hayashizaki K., Nakayama T.
    • Organizer
      The 2nd Chiba University-UC San Diego Symposium "Mucosal Immunology, Allergy and Vaccine"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Myosin light chains 9 and 12 are functional ligands for CD69 that regulate airway inflammation.2017

    • Author(s)
      Hayashizaki, K., Kimura, M.Y., Igi, A., and Nakayama, T.
    • Organizer
      7th International Workshop of Kyoto T Cell Conference
    • Place of Presentation
      京都大学医学部・芝蘭会館(京都府京都市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Myosin light chain 9 and 12 are functional ligands for CD69 that regulate airway inflammation2017

    • Author(s)
      Kimura M.Y., Hayashizaki K., Nakayama T.
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Timing and duration of MHC-I positive selection and CD8 lineage choice in the thymus.2016

    • Author(s)
      Kimura M.Y.
    • Organizer
      NIH Thymus Symposium
    • Place of Presentation
      NIH, Bethesda, USA
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Timing and duration of MHC-I positive selection signals in the thymus reveal a novel compensatory signaling mechanism that prevents lineage fate errors.2016

    • Author(s)
      Kimura, M.Y., Nakayama, T., and Singer, A.
    • Organizer
      第45回日本免疫学会総会・学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Roles of IL-2 on Th9 cell differentiation2015

    • Author(s)
      Sarkar, H. M., Yagi, R., Nakajima, T., Kimura, M., Nakayama, T., and Zhu, J.
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌コンベンションセンター (北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Molecular basis for acquisition of helper function during thymocyte development2015

    • Author(s)
      Motoko Y. Kimura, Toshinori Nakayama and Alfred Singer
    • Organizer
      第25回 Kyoto T Cell Conference
    • Place of Presentation
      京都大学芝蘭会館  (京都府京都市)
    • Year and Date
      2015-05-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Strong TCR signaling prolongs lineage uncertainty during MHC-I specific positive selection2015

    • Author(s)
      Kimura, M., Nakayama, T., and Singer, A.
    • Organizer
      Immunology 2015 AAI Annual Meeting
    • Place of Presentation
      New Orleans (U.S.A.)
    • Year and Date
      2015-05-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular basis for acquisition of helper function during thymocyte development2015

    • Author(s)
      Motoko Y. Kimura, Miho Shinzawa, Ruth Etzensperger, Ryoji Yagi, Koji Hayashizaki, Akemi Igi, Toshinori Nakayama and Alfred Singer
    • Organizer
      Venice Thymus Meeting 2015
    • Place of Presentation
      Venice (Italy)
    • Year and Date
      2015-04-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Remarks] 千葉大学大学院医学研究院免疫発生学

    • URL

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

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Remarks] 千葉大学大学院医学研究院免疫発生学ホームページ

    • URL

      http://www.m.chiba-u.ac.jp/class/meneki/index.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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