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Aire expressing ILC3-like cells in the lymph node display potent APC features

Research Project

Project/Area Number 18K15182
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Yamano Tomoyoshi  金沢大学, 医学系, 助教 (40724183)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords免疫寛容 / Aire / 胸腺 / 末梢性免疫寛容 / 自然リンパ球
Outline of Final Research Achievements

APECED is an autoimmune disease caused by mutations in the Aire gene, which is expressed specifically in thymic medullary epithelial cells. Aire is essential for the central tolerance induction in the thymus.
In this study, I discovered Aire-expressing cells (AireILC3-like cells) in LN, which have a characteristic of type 3 innate lymphocyte. I showed that the development of AireILC3-like cells is RORrt-dependent, and AireILC3-like cells induce peripheral tolerance to self-reactive T cells in peripheral lymphoid tissues.

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患は本来自己を守るための免疫系が自己を攻撃してしまうためにおこる疾患で、その根本的な治療法は未だ確立されておらず、また多くの場合その発症の原因がわかっていない。
Aire遺伝子は免疫寛容に必須の遺伝子で、最近リンパ節にもAireの発現が報告されていたが、どの細胞がAireを発現しているかは議論があった。本研究はリンパ節でAireを発現する細胞は何であるのかという議論に終止符を打つものであり,免疫寛容の一部を担う新たな細胞を発見したものである。このような知見の積み重ねによって,将来,原因が不明である膠原病や自己免疫疾患に対する原因解明およびその治療法の確立につながることが期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (4 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] IMG of the Czech Academy of Sciences(チェコ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Munich(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] IMG of the Czech Academy of Sciences(チェコ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Munich(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Aire-expressing ILC3-like cells in the lymph node display potent APC features2019

    • Author(s)
      Yamano Tomoyoshi、Dobes Jan、Voboril Matous、Steinert Madlen、Brabec Tomas、Zietara Natalia、Dobesova Martina、Ohnmacht Caspar、Laan Martti、Peterson Part、Benes Vladimir、Sedlacek Radislav、Hanayama Rikinari、Kolar Michal、Klein Ludger、Filipp Dominik
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 印刷中 Issue: 5 Pages: 1027-1037

    • DOI

      10.1084/jem.20181430

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Function and Immunogenicity of Gene-corrected iPSC-derived Hepatocyte-Like Cells in Restoring Low Density Lipoprotein Uptake in Homozygous Familial Hypercholesterolemia.2019

    • Author(s)
      Okada H, Nakanishi C, Yoshida S, Shimojima M, Yokawa J, Mori M, Tada H, Yoshimuta T, Hayashi K, Yamano T, Hanayama R, Yamagishi M, Kawashiri MA
    • Journal Title

      Scientific reports

      Volume: 9 Issue: 1 Pages: 4695-4695

    • DOI

      10.1038/s41598-019-41056-w

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] B cells latently infected with murine gammaherpesvirus 68 (MHV‐68) are present in the mouse thymus?A step toward immune evasion?2018

    • Author(s)
      Yamano Tomoyoshi、Steinert Madlen、Steer Beatrix、Klein Ludger、Hammerschmidt Wolfgang、Adler Heiko
    • Journal Title

      European Journal of Immunology

      Volume: 49 Issue: 2 Pages: 351-352

    • DOI

      10.1002/eji.201847886

    • Related Report
      2018 Research-status Report
  • [Journal Article] Myoferlin-Mediated Lysosomal Exocytosis Regulates Cytotoxicity by Phagocytes2018

    • Author(s)
      Miyatake Yuji、Yamano Tomoyoshi、Hanayama Rikinari
    • Journal Title

      The Journal of Immunology

      Volume: 201 Issue: 10 Pages: 3051-3057

    • DOI

      10.4049/jimmunol.1800268

    • Related Report
      2018 Research-status Report
  • [Presentation] 胸腺細胞外小胞がT細胞分化に与える影響の解析2019

    • Author(s)
      山野友義
    • Organizer
      京都T細胞学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 胸腺細胞外小胞がT細胞分化に与える影響の解析2019

    • Author(s)
      山野友義
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] A role of extracelluar vesicle in T cell development2019

    • Author(s)
      Tomoyoshi Yamano
    • Organizer
      The 48th annual meeting for Japanesse society for Immunology
    • Related Report
      2019 Annual Research Report
  • [Presentation] A RORγt-dependent innate lymphoid cell-type in secondary lymphoid organs expresses Aire and presents endogenously expressed antigen for T cell tolerance2018

    • Author(s)
      Tomoyoshi Yamano
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] 免疫寛容に関わる細胞の特定に世界に先駆けて成功!

    • URL

      https://www.kanazawa-u.ac.jp/rd/65824

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2021-02-19  

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