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

Understanding the mechanisms of the breakdown of self-tolerance initiated from the thymus

Research Project

Project/Area Number 18K19442
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionKyoto University

Principal Investigator

Hamazaki Yoko  京都大学, iPS細胞研究所, 教授 (10362477)

Project Period (FY) 2018-06-29 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords胸腺 / 中枢性自己寛容 / ハッサル小体 / 胸腺髄質 / 自己寛容 / 胸腺上皮細胞 / 自己免疫疾患
Outline of Final Research Achievements

Hassall corpuscle (HC) is a characteristic keratinized structure within the thymic medulla, which is crucial for establishing central T-cell self-tolerance. In this study, we found that the medullary thymic epithelial cells constituting HCs undergo cellular senescence in a steady state and constantly express inflammatory cytokines such as CXCL5 and IL-1 family as SASP factors. In addition, a mouse strain exhibiting systemic autoimmune disease (NZB/W F1) shows HC hyperplasia, with high activation levels of neutrophils and pDCs, as well as T cells in the thymus. Administration of anti-Gr-1 antibody and removal of neutrophils, which are assumed to react to CXCL5, suppressed pDC activation and type I IFN production. These results suggest that T cells are activated in the thymus by HC hyperplasia, suggesting a role in initiating autoimmunity.

Academic Significance and Societal Importance of the Research Achievements

HCを構成する髄質上皮細胞を純化しその遺伝子発現の特徴を明らかにすることで、長らく組織学定義にとどまっていた胸腺髄質のHCを分子細胞レベルで定義することができた。また、自己免疫疾患モデルマウスにおいてHCの過形成や低形成が認められること、HCの過形成が胸腺内好中球やpDCを活性化し、おそらくはそれを介して胸腺内でT細胞が活性化している可能性を示唆することができた。本研究は、自己免疫疾患発症メカニズムの解明とその介入方法開発の一助となることが期待される。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (43 results)

All 2023 2022 2021 2020 2019 2018 Other

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 12 results) Presentation (23 results) (of which Int'l Joint Research: 9 results,  Invited: 23 results) Remarks (5 results)

  • [Journal Article] Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination2023

    • Author(s)
      Jo Norihide、Hidaka Yu、Kikuchi Osamu、Fukahori Masaru、Sawada Takeshi、Aoki Masahiko、Yamamoto Masaki、Nagao Miki、Morita Satoshi、Nakajima Takako E.、Muto Manabu、Hamazaki Yoko
    • Journal Title

      Nature Aging

      Volume: 3 Issue: 1 Pages: 82-92

    • DOI

      10.1038/s43587-022-00343-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8+ T Cells in Unexposed Individuals2021

    • Author(s)
      Jo Norihide、Zhang Rui、Ueno Hideki、Yamamoto Takuya、Weiskopf Daniela、Nagao Miki、Yamanaka Shinya、Hamazaki Yoko
    • Journal Title

      Frontiers in Aging

      Volume: 2 Pages: 719342-719342

    • DOI

      10.3389/fragi.2021.719342

    • NAID

      120007141692

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intravital Imaging Identifies the VEGF?TXA2 Axis as a Critical Promoter of PGE2 Secretion from Tumor Cells and Immune Evasion2021

    • Author(s)
      Konishi Yoshinobu、Ichise Hiroshi、Watabe Tetsuya、Oki Choji、Tsukiji Shinya、Hamazaki Yoko、Murakawa Yasuhiro、Takaori-Kondo Akifumi、Terai Kenta、Matsuda Michiyuki
    • Journal Title

      Cancer Research

      Volume: 81 Issue: 15 Pages: 4124-4132

    • DOI

      10.1158/0008-5472.can-20-4245

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Selective expression of claudin-5 in thymic endothelial cells regulates the blood-thymus barrier and T-cell export2021

    • Author(s)
      Takahiro Nagatake, Yan-Chun Zhao, Takeshi Ito, Masahiko Itoh, Kohei Kometani, Mikio Furuse, Azusa Saika, Eri Node, Jun Kunisawa, Nagahiro Minato, Yoko Hamazaki
    • Journal Title

      International Immunology

      Volume: 33(3) Issue: 3 Pages: 171-182

    • DOI

      10.1093/intimm/dxaa069

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone Marrow Endothelial Cells Take Up Blood-Borne Immune Complexes via Fcγ Receptor IIb2 in an Erythropoietin-Dependent Manner2020

    • Author(s)
      Ito Takeshi、Kometani Kohei、Minato Nagahiro、Hamazaki Yoko
    • Journal Title

      The Journal of Immunology

      Volume: 205 Issue: 8 Pages: 2008-2015

    • DOI

      10.4049/jimmunol.1901101

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Physiology and pathology of T-cell aging2020

    • Author(s)
      Minato Nagahiro、Hattori Masakazu、Hamazaki Yoko
    • Journal Title

      International Immunology

      Volume: 32 Issue: 4 Pages: 223-231

    • DOI

      10.1093/intimm/dxaa006

    • NAID

      120006936327

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets2019

    • Author(s)
      Li Hongtu、Neelankal John Abraham、Nagatake Takahiro、Hamazaki Yoko、Jiang Fang‐Xu
    • Journal Title

      FEBS Open Bio

      Volume: 10 Issue: 1 Pages: 28-40

    • DOI

      10.1002/2211-5463.12735

    • NAID

      120006784462

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Propagermanium Induces NK Cell Maturation and Tends to Prolong Overall Survival of Patients With Refractory Cancer2019

    • Author(s)
      KIKUCHI SHOJIRO、NOGUCHI KAZUMA、WAKAI KEIKO、HAMAZAKI YOKO、TOZAWA KATSUYUKI、JOMORI TAKAHITO、SASAKO MITSURU、MIWA HIROTO
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 9 Pages: 4687-4698

    • DOI

      10.21873/anticanres.13651

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clonogenic Culture of Mouse Thymic Epithelial Cells2019

    • Author(s)
      Sekai Miho、Wang Jianwei、Hamazaki Yoko
    • Journal Title

      Methods Mol Biol.

      Volume: 2048 Pages: 143-153

    • DOI

      10.1007/978-1-4939-9728-2_15

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rap1 signal modulators control the maintenance of hematopoietic progenitors in bone marrow and adult long-term hematopoiesis2019

    • Author(s)
      Imai T, Tanaka H, Hamazaki Y, Minato N
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 4 Pages: 1317-1330

    • DOI

      10.1111/cas.13974

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An improved clonogenic culture method for thymic epithelial cells2019

    • Author(s)
      Sekai Miho、Wang Jianwei、Minato Nagahiro、Hamazaki Yoko
    • Journal Title

      Journal of Immunological Methods

      Volume: 467 Pages: 29-36

    • DOI

      10.1016/j.jim.2019.02.003

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hassall’s corpuscles with cellular-senescence features maintain IFNα production through neutrophils and pDC activation in the thymus2018

    • Author(s)
      Wang Jianwei、Sekai Miho、Matsui Takeshi、Fujii Yosuke、Matsumoto Mitsuru、Takeuchi Osamu、Minato Nagahiro、Hamazaki Yoko
    • Journal Title

      International Immunology

      Volume: 31 Issue: 3 Pages: 127-139

    • DOI

      10.1093/intimm/dxy073

    • NAID

      120007164929

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Live-Cell FRET Imaging Reveals a Role of Extracellular Signal-Regulated Kinase Activity Dynamics in Thymocyte Motility2018

    • Author(s)
      Konishi Y, Terai K, Furuta Y, Kiyonari H, Abe T, Ueda Y, Kinashi T, Hamazaki Y, Takaori-Kondo A, and Matsuda M
    • Journal Title

      iScience

      Volume: 10 Pages: 98-113

    • DOI

      10.1016/j.isci.2018.11.025

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CXCR3high CD8+ T cells with na?ve phenotype and high capacity for IFN-γ production are generated during homeostatic T-cell proliferation2018

    • Author(s)
      Kato Aiko、Takaori-Kondo Akifumi、Minato Nagahiro、Hamazaki Yoko
    • Journal Title

      European Journal of Immunology

      Volume: 48 Issue: 10 Pages: 1663-1678

    • DOI

      10.1002/eji.201747431

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] T cell aging and immunosenescence2018

    • Author(s)
      濱崎 洋子、湊 長博
    • Journal Title

      Leading Author's

      Volume: 7 Pages: e005

    • DOI

      10.7875/leading.author.7.e005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Age-related and individual heterogeneity of immune responses to SARS-CoV-2 mRNA vaccine2022

    • Author(s)
      Yoko Hamazaki
    • Organizer
      第51回日本免疫学会学術集会 国際シンポジウム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Immunity among Aging Populations; A New Research Area Emerging from the COVID-19 Pandemic2022

    • Author(s)
      濱崎 洋子
    • Organizer
      第51回日本免疫学会学術集会 オーバーヴュートーク
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 免疫の老化と再生医学2022

    • Author(s)
      濱崎 洋子
    • Organizer
      鳥取大学医学部セミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Age-related and individual heterogeneity of immune responses to SARS-CoV-2 mRNA vaccine2022

    • Author(s)
      Yoko Hamazaki
    • Organizer
      OIST-Kyoto Univesity Joint workshop
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vitro development and maturation of human thymic epithelial cells from iPSCs2022

    • Author(s)
      Yoko Hamazaki
    • Organizer
      Stemness, Regeneration and Immunity: from development to therapy, The Francis Crick Institute symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 免疫の老化:メカニズムの理解と健康長寿へのチャレンジ2022

    • Author(s)
      濱崎 洋子
    • Organizer
      第8回京都大学―稲盛財団合同 京都賞シンポジウム 免疫系による個体統御
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 免疫の老化と再生医学2022

    • Author(s)
      濱崎 洋子
    • Organizer
      東京都港区麻布赤坂歯科医師会・CiRA共催シンポジウム 再生医学が未来を拓く ~歯の細胞とiPS細胞の可能性~
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] T細胞の加齢変化とその意義2021

    • Author(s)
      濱崎 洋子
    • Organizer
      第73回日本細胞生物学会 シンポジウム「老化機構の解明と制御を介して―免疫と幹細胞の話題を中心に」
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] T細胞老化と胸腺退縮2021

    • Author(s)
      濱崎 洋子
    • Organizer
      第54回日本眼炎症学会・第63回日本コンタクトレンズ学会総会 合同シンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 免疫の老化と新型コロナウイルス感染症2021

    • Author(s)
      濱崎 洋子
    • Organizer
      学校法人洛南高等学校 同附属中学校 講演会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] The Impact of Aging on SARS-CoV-2 Reactive T Cells2021

    • Author(s)
      Yoko Hamazaki
    • Organizer
      Cold Spring Harbor Lab meeting COVID/SARS CoV2 Rapid Research Reports #5
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] T cell aging due to thymic involution2020

    • Author(s)
      Yoko Hamazaki
    • Organizer
      日本分子生物学会 国際シンポジウム T cell aging and exhaustion: from a perspective of metabolism/
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 免疫応答 ウイルスから老化まで ―T細胞を中心に―2020

    • Author(s)
      濱崎 洋子
    • Organizer
      日本抗加齢医学会 専門医・指導士認定委員会講習会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] T細胞老化と胸腺退縮2020

    • Author(s)
      濱崎 洋子
    • Organizer
      第72回日本細胞生物学会大会 シンポジウム 老化機構の解明と制御を目指して- 炎症との接点から考える-
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Impacts of thymic involution on T cell aging and immunosenescence2020

    • Author(s)
      Yoko Hamazaki
    • Organizer
      RIKEN Aging Project Meeting 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] T cell aging due to thymic involution: role in immunosenescence and possible interventions2019

    • Author(s)
      Yoko Hamazaki
    • Organizer
      France - Japan Symposium "Implications of Senescence in Age Related Disorders : Towards Healthy Aging"
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Impacts of thymic involution on T cell aging and immunosenescence2019

    • Author(s)
      濱崎 洋子
    • Organizer
      RIKEN Aging Project Meeting 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 胸腺上皮幹細胞活性の制御機構2019

    • Author(s)
      濱崎 洋子
    • Organizer
      第4回京都皮膚基礎研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 胸腺退縮とT細胞老化2019

    • Author(s)
      濱崎 洋子
    • Organizer
      第51回ヒューマンサイエンス総合研究セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 免疫システムの形成と破綻そして再構築-T細胞とその産生臓器 胸腺組織を中心に―2018

    • Author(s)
      濱崎 洋子
    • Organizer
      大阪市立大学 セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 自己と非自己を見分ける免疫の仕組みと加齢変化2018

    • Author(s)
      濱崎 洋子
    • Organizer
      京都大学丸の内セミナー(第99回)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 胸腺退縮と免疫老化2018

    • Author(s)
      濱崎 洋子
    • Organizer
      千里ライフサイエンスセミナーM1「老化メカニズムと疾患制御」
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 胸腺退縮とT細胞老化2018

    • Author(s)
      濱崎 洋子
    • Organizer
      第18回日本抗加齢医学会総会 シンポジウム 免疫老化の最前線
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] 京都大学iPS細胞研究所HP

    • URL

      https://www.cira.kyoto-u.ac.jp/j/research/hamazaki_summary.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 京都大学iPS細胞研究所HP 濱崎研HP

    • URL

      https://hmy.cira.kyoto-u.ac.jp/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 京都大学医学研究科 免疫生物学

    • URL

      http://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-186/

    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Remarks] 京都大学iPS細胞研究所 未来生命科学開拓部門

    • URL

      https://www.cira.kyoto-u.ac.jp/j/research/hamazaki_summary.html

    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Remarks] 京都大学iPS細胞研究所 京都大学医学研究科 免疫生物学 濱崎研究室

    • URL

      http://www.cira.kyoto-u.ac.jp/hmy/

    • Related Report
      2020 Research-status Report

URL: 

Published: 2018-07-25   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi