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Understanding the role of Hassall's body abnormalities in the breakdown of self-tolerance

Research Project

Project/Area Number 18H02640
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 InstitutionKyoto University

Principal Investigator

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

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords胸腺 / 自己寛容 / ハッサル小体 / 胸腺上皮細胞 / 自己免疫疾患
Outline of Final Research Achievements

The thymic medulla is an anatomical region involved in establishing central self-tolerance. Hassall corpuscle (HC) is a characteristic keratinized structure within the thymic medulla; however, the role of HC on central tolerance is not well understood. In this study, we performed gene expression analysis of purified HC-constituting medullary thymic epithelial cells (mTEC). We revealed that HC-mTEC undergo cellular senescence in a steady state and express high levels of inflammatory molecules such as CXCL5 and IL-1 family members. Depletion of neutrophils, which express the CXCL5 receptor, suppresses the activation of pDCs in the thymic medulla. These results suggest that neutrophils are recruited and activated in response to CXCL5 produced as part of SASP from HC mTECs, and he activated neutrophils may induce pDCs activation in the thymic medulla. In summary, we succeeded in defining HC constitutive mTEC at the molecular level.

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を分子レベルで定義することができた。今後、HCの過形成や低形成が胸腺髄質機能の異常制御や中枢性自己寛容の破綻に果たす役割を理解することで、自己免疫疾患発症メカニズムの一端が明らかになることが期待される。

Report

(5 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (27 results)

All 2022 2021 2019 2018 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 6 results,  Invited: 10 results) Remarks (4 results)

  • [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
      2021 Annual Research 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 Annual Research Report 2018 Annual Research 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 Annual Research Report 2018 Annual Research 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 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research 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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Age-related and individual heterogeneity of immune responses to SARS-CoV-2 mRNA vaccine2022

    • Author(s)
      Yoko Hamzaki
    • Organizer
      第51回日本免疫学会学術集会 国際シンポジウム 老化と免疫
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / 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
      2020 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
      2020 Annual Research 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 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] T細胞の発生と機能、そして老化2019

    • Author(s)
      濱崎 洋子
    • Organizer
      2019年度市民セミナー 第35回西宮市ライフサイエンスセミナー 総合テーマ「免疫のライフサイエンス~最近の話題と免疫疾患~」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 中学時代から京都大学iPS細胞研究所(CiRA)まで2019

    • Author(s)
      濱崎 洋子
    • Organizer
      JST H31女子中高生理系進路選択支援プログラム「輝け未来の私!山陰ガールズプロジェクト」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Road to the rejuvenation and reconstitution of the thymic microenvironment2019

    • Author(s)
      濱崎 洋子
    • Organizer
      第48回日本免疫学会学術集会 国際シンポジウム Lympho-hematopoiesis and its niche microenvironments オーバービュートーク
    • Related Report
      2019 Annual Research 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 招待講演
    • Related Report
      2019 Annual Research 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 Annual Research 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―2019

    • Author(s)
      濱崎洋子
    • Organizer
      大阪市立大学 セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] 自己と非自己を見分ける免疫の仕組みと加齢変化-T細胞とその産生臓器 胸腺を中心に―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 Annual Research Report
  • [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 Annual Research Report
  • [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 Annual Research Report
  • [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
      2020 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
      2020 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
      2018 Annual Research 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
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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