• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular basis of immune homeostasis originating from the thymus

Research Project

Project/Area Number 20H03464
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionChiba University

Principal Investigator

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

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords制御性T細胞 / CD69 / γδT細胞 / 胸腺 / 恒常性維持 / アゴニスト選択
Outline of Research at the Start

制御性T(Treg)細胞をはじめとしたアゴニスト選択によって分化誘導される細胞群は、自己免疫疾患制御、生体の恒常性維持、がん免疫、各種炎症反応等に重要な働きをすることが知られているが、その分化機構、各種サブセットの存在、機能の詳細は不明点が多い。一方、CD69分子は、アゴニスト選択によって分化誘導される細胞群に恒常的に発現しており、その分化、機能に重要な働きをすることが示唆される。本申請研究では、「Treg細胞」「CD69」「胸腺内アゴニスト選択」という三つのキーワードに基づいて研究を進め、生体の恒常性維持機構と恒常性維持に重要な各種T細胞の分化機構と機能についての新規のメカニズム解析を行う。

Outline of Final Research Achievements

Regulatory T cells and Innate-like T cells that are differentiated by the thymic agonist selection such as natural killer T cells and γδT cells, are known to play important roles in regulating autoimmune diseases, tissue homeostasis, cancer immunity, and various inflammatory responses. However, the details of their subsets, differentiation mechanisms, and functions remain unclear. In this study, we focused on the CD69 molecule, which has been known as an activation marker of leukocytes, and found that CD69 regulates the differentiation and function of the regulatory T cells and innate-like T cells. CD69 expressed by T cells was found to be involved in tissue homeostasis and anti-tumor immune responses.

Academic Significance and Societal Importance of the Research Achievements

制御性T細胞や自然免疫型T細胞(NKT細胞、γδT細胞など)は、感染に対する免疫応答や抗腫瘍免疫応答に働くだけでなく、組織の恒常性維持に寄与することが明らかとなってきた。本研究では、CD69分子が、これらの細胞の分化・維持・機能を制御することを見出した。この事実は、将来的に、ヒトの炎症性疾患や腫瘍に対する新たな治療法開発に貢献できる可能性を示唆する。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (31 results)

All 2023 2022 2021 2020 Other

All Journal Article (14 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (15 results) (of which Int'l Joint Research: 10 results,  Invited: 8 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Increased Myosin light chain 9 expression during Kawasaki disease vasculitis2023

    • Author(s)
      Kobayashi Hironobu、Kimura Motoko Y.、Hasegawa Ichita、Suganuma Eisuke、Ikehara Yuzuru、Azuma Kazuhiko、Ito Toshihiro、Ebata Ryota、Kurashima Yosuke、Kawasaki Yohei、Shiko Yuki、Saito Naoki、Iwase Hirotaro、Lee Youngho、Noval Rivas Magali、Arditi Moshe、Zuka Masahiko、Hamada Hiromichi、Nakayama Toshinori
    • Journal Title

      Frontiers in Immunology

      Volume: 13

    • DOI

      10.3389/fimmu.2022.1036672

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD69 imposes tumor-specific CD8+ T cell fate in tumor-draining lymph nodes2023

    • Author(s)
      Koyama-Nasu Ryo、Kimura Motoko Y.、 Kiuchi Masahiro、 Aoki Ami、Wang Yangsong, Mita Yukiyoshi、Hasegawa Ichita、Endo Yukihiro、Onodera Atsushi、Hirahara Kiyoshi、 Motohashi Shinichiro、Nakayama Toshinori
    • Journal Title

      Cancer Immunology Research

      Volume: -

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and Histological Effects of Partial Blood Flow Impairment in Vascularized Lymph Node Transfer2022

    • Author(s)
      Shinsuke Akita, Yuzuru Ikehara, Minami Arai, Hideki Tokumoto, Yoshihisa Yamaji, Kazuhiko Azuma, Yoshitaka Kubota, Hideaki Haneishi, Motoko Y Kimura, Nobuyuki Mitsukawa
    • Journal Title

      J Clin Med

      Volume: 11 Issue: 14 Pages: 4052-4052

    • DOI

      10.3390/jcm11144052

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity2022

    • Author(s)
      Iwamura Chiaki、Hirahara Kiyoshi、Kiuchi Masahiro、Ikehara Sanae、Azuma Kazuhiko、Shimada Tadanaga、Kuriyama Sachiko、Ohki Syota、Yamamoto Emiri、Inaba Yosuke、Shiko Yuki、Aoki Ami、Kokubo Kota、et al.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 33 Pages: 2203437119-2203437119

    • DOI

      10.1073/pnas.2203437119

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The cellular and molecular basis of CD69 function in anti-tumor immunity2022

    • Author(s)
      Koyama-Nasu Ryo、Wang Yangsong、Hasegawa Ichita、Endo Yukihiro、Nakayama Toshinori、Kimura Motoko Y
    • Journal Title

      International Immunology

      Volume: 34 Issue: 11 Pages: 555-561

    • DOI

      10.1093/intimm/dxac024

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD69-Myl9システムと炎症性疾患2022

    • Author(s)
      木村元子、中山俊憲
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 77 Pages: 517-520

    • Related Report
      2022 Annual Research Report
  • [Journal Article] IFNγ suppresses the expression of GFI1 and thereby inhibits Th2 cell proliferation2021

    • Author(s)
      Sarkar Murshed H.、Yagi Ryoji、Endo Yukihiro、Koyama-Nasu Ryo、Wang Yangsong、Hasegawa Ichita、Ito Toshihiro、Junttila Ilkka S.、Zhu Jinfang、Kimura Motoko Y.、Nakayama Toshinori
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 11 Pages: e0260204-e0260204

    • DOI

      10.1371/journal.pone.0260204

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD4+ T cells in inflammatory diseases: pathogenic T-helper cells and the CD69-Myl9 system2021

    • Author(s)
      Nakayama Toshinori、Hirahara Kiyoshi、Kimura Motoko Y、Iwamura Chiaki、Kiuchi Masahiro、Kokubo Kota、Onodera Atsushi、Hashimoto Kahoko、Motohashi Shinichiro
    • Journal Title

      International Immunology

      Volume: 33(12) Issue: 12 Pages: 699-704

    • DOI

      10.1093/intimm/dxab053

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myosin Light Chain 9/12 Regulates the Pathogenesis of Inflammatory Bowel Disease2021

    • Author(s)
      Yokoyama Masaya、Kimura Motoko Y.、Ito Toshihiro、Hayashizaki Koji、Endo Yukihiro、Wang Yangsong、Yagi Ryoji、Nakagawa Tomoo、Kato Naoya、Matsubara Hisahiro、Nakayama Toshinori
    • Journal Title

      Frontiers in Immunology

      Volume: 11

    • DOI

      10.3389/fimmu.2020.594297

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 胸腺内iNKT細胞分化機構とCD69の役割2021

    • Author(s)
      木村元子
    • Journal Title

      血液内科

      Volume: 82(1)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Essential Role for CD30-Transglutaminase 2 Axis in Memory Th1 and Th17 Cell Generation2020

    • Author(s)
      Suzuki Akane S.、Yagi Ryoji、Kimura Motoko Y.、Iwamura Chiaki、Shinoda Kenta、Onodera Atsushi、Hirahara Kiyoshi、Tumes Damon J.、Koyama-Nasu Ryo、Iismaa Siiri E.、Graham Robert M.、Motohashi Shinichiro、Nakayama Toshinori
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 1536-1536

    • DOI

      10.3389/fimmu.2020.01536

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner2020

    • Author(s)
      Aoki Takahiro、Takami Mariko、Takatani Tomozumi、Motoyoshi Kiwamu、Ishii Ayana、Hara Ayaka、Toyoda Takahide、Okada Reona、Hino Moeko、Koyama‐Nasu Ryo、Kiuchi Masahiro、Hirahara Kiyoshi、Kimura Motoko Y.、Nakayama Toshinori、Shimojo Naoki、Motohashi Shinichiro
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 7 Pages: 2223-2233

    • DOI

      10.1111/cas.14428

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation of Pathogenic Th17 Cells Is Negatively Regulated by Let-7 MicroRNAs in a Mouse Model of Multiple Sclerosis2020

    • Author(s)
      Angelou Constance C.、Wells Alexandria C.、Vijayaraghavan Jyothi、Dougan Carey E.、Lawlor Rebecca、Iverson Elizabeth、Lazarevic Vanja、Kimura Motoko Y.、Peyton Shelly R.、Minter Lisa M.、Osborne Barbara A.、Pobezinskaya Elena L.、Pobezinsky Leonid A.
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 3125-3125

    • DOI

      10.3389/fimmu.2019.03125

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] T細胞性免疫のエフェクタ-機能のメカニズム 生体防御におけるT細胞の機能2020

    • Author(s)
      中山俊憲、木村元子、八木良二
    • Journal Title

      基礎免疫学 原著第6版ー免疫系の機能とその異常

      Volume: - Pages: 111-127

    • Related Report
      2020 Annual Research Report
  • [Presentation] CD69 biology and pathology2023

    • Author(s)
      Kimura Motoko Y.
    • Organizer
      International Symposium for Future Mucosal Vaccines
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CD69 regulates anti-tumor CD8T cell responses2023

    • Author(s)
      Koyama-Nasu Ryo、Wang Yangsong、Endo Yukihiro、Hasegawa Ichita、Ueno Tatsuya、Mita Yukiyoshi、Motohashi Shinichiro、Nakayama Toshinori、Kimura Motoko Y.
    • Organizer
      International Symposium for Future Mucosal Vaccines
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The essential role of central tolerance in tumor progression2023

    • Author(s)
      Wang Yangsong、Koyama-Nasu Ryo、 Hasegawa Ichita、Endo Yukihiro、Kano Shunka, Kimura Motoko Y.
    • Organizer
      International Symposium for Future Mucosal Vaccines
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of CD69 on thymic regulatory T cell development2023

    • Author(s)
      Endo Yukihiro、Ueno Tatsuya、Hasegawa Ichita、Wang Yangsong、Koyama-Nasu Ryo、 Kimura Motoko Y.
    • Organizer
      International Symposium for Future Mucosal Vaccines
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CD69 biology and pathology2022

    • Author(s)
      Kimura Motoko Y.
    • Organizer
      The 95th Annual Meeting of the Japanese Biochemical Society
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] T細胞を中心とした抗腫瘍免疫応答の包括的理解とその治療戦略基盤の創生2022

    • Author(s)
      木村元子
    • Organizer
      千葉大学 国際高等研究基幹(IAAR)キックオフシンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胸腺内制御性R細胞分化におけるCD69の役割2022

    • Author(s)
      遠藤将大、上野達矢、長谷川一太、Wang Yangsong、那須亮、木村元子
    • Organizer
      第31回Kyoto T Cell Congerence学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腫瘍特異的CD8T細胞の分化運命決定機構2022

    • Author(s)
      那須亮、Wang Yangsong、長谷川一太、遠藤将大、中山俊憲、木村元子
    • Organizer
      第31回Kyoto T Cell Congerence学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] CD69 regulates anti-tumor CD8T cell responses2022

    • Author(s)
      Koyama-Nasu Ryo、Wang Yangsong、Endo Yukihiro、Hasegawa Ichita、Ueno Tatsuya、Mita Yukiyoshi、Motohashi Shinichiro、Nakayama Toshinori、Kimura Motoko Y.
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The essential role of central tolerance in tumor progression2022

    • Author(s)
      Wang Yangsong、Koyama-Nasu Ryo、 Hasegawa Ichita、Endo Yukihiro、Kano Shunka, Kimura Motoko Y.
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of CD69 on thymic regulatory T cell development2022

    • Author(s)
      Endo Yukihiro、Ueno Tatsuya、Hasegawa Ichita、Wang Yangsong、Koyama-Nasu Ryo、 Kimura Motoko Y.
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多彩な働きをするT細胞の分化・機能と疾患制御2022

    • Author(s)
      木村元子
    • Organizer
      第6回 千葉大学 膜タンパク質研究センター×量子科学技術研究開発機構 量子生命科学研究所 合同勉強会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CD69 regulates anti-tumor immunity2021

    • Author(s)
      Kimura M., Nasu R., Mita Y., Wang Y., Endo Y., Hasegawa I., Motohashi S., Nakayama T.
    • Organizer
      The 50th Annual Meeting of the Japanese Society for Immunology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CD69-Myl9システムと炎症制御2021

    • Author(s)
      木村元子, 横山将也, 小林弘信, 林﨑浩史, 遠藤将大, Wang Yangsong, 長谷川一太, 那須亮, 中山俊憲
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CD69 Biology and Pathology2020

    • Author(s)
      Kimura M.Y., Koyama-Nasu, R., Mita Y., Hayashizaki, K. and Nakayama T.
    • Organizer
      11th International Symposium of IFReC, Immunology at the Forefront
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 分子細胞免疫学 原著第10版2022

    • Author(s)
      Abul K. Abbas、Andrew H. Lichtman、Shiv Pillai、中尾篤人(翻訳 木村元子他)
    • Total Pages
      650
    • Publisher
      エルゼビア・ジャパン
    • ISBN
      4860346769
    • Related Report
      2022 Annual Research Report
  • [Remarks] 千葉大学大学院医学研究院 免疫発生学HP

    • URL

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

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi