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Pathophysiological relevance of intracellular cholesterol metabolism in autoimmune diseases

Research Project

Project/Area Number 17K16146
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionNagoya University

Principal Investigator

Ito Ayaka  名古屋大学, 環境医学研究所, 助教 (80508333)

Research Collaborator Tontonoz Peter  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords自己免疫疾患 / 免疫細胞 / 脂質代謝 / 細胞内代謝 / 免疫代謝 / コレステロール / 免疫細胞機能 / 抗原提示細胞
Outline of Final Research Achievements

In this study, we analyzed genetic and drug-induced SLE model mice and elucidated that titers of autoantibodies and deposition of immunoglobulin in kidney were increased in the SLE model mice compared to the control mice. We also found that lipid content in immune cells was higher in SLE than control mice, and which was observed at the beginning of the development of SLE. On the other hand, there was no difference in serum lipid profile and hepatic gene expression of lipid metabolism between SLE and control mice. Administration of an agent to improve systemic lipid metabolism prevented the development of SLE. These findings suggest that lipid accumulation in immune cells is cell intrinsic effect and improvement of systemic lipid metabolism could be beneficial in the setting of autoimmune disease.

Academic Significance and Societal Importance of the Research Achievements

本研究により、SLEの発症や進展過程において、早期から細胞自律的な脂質蓄積が起こることが明らかになり、近年注目されている免疫代謝領域における新たな発見となった。脂質代謝改善薬の投与がSLE発症を抑制したことより、今後は、全身とは独立して制御される免疫細胞内の脂質蓄積のメカニズムを解明し、免疫細胞内の脂質の量と質の変化に着目して、より詳細に研究を進める。SLEの病態メカニズムを明らかにするとともに、SLEの早期診断マーカーや食事療法の開発を目指したい。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA2018

    • Author(s)
      1.Sallam T, Jones M, Thomas BJ, Wu X, Gilliland T, Qian K, Eskin A, Casero D, Zhang Z, Sandhu J, Salisbury D, Rajbhandari P, Civelek M, Hong C, Ito A, Liu X, Daniel B, Lusis AJ, Whitelegge J, Nagy L, Castrillo A, Smale S and Tontonoz P.
    • Journal Title

      Nature Medicine

      Volume: 24 Issue: 3 Pages: 304-312

    • DOI

      10.1038/nm.4479

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 自己免疫疾患発症における細胞内コレステロール代謝の意義2018

    • Author(s)
      伊藤綾香、Cynthia Hong、Peter Tontonoz、菅波孝祥
    • Organizer
      第55回日本臨床分子医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 自己免疫疾患発症における細胞内コレステロール代謝の意義2018

    • Author(s)
      伊藤綾香、Cynthia Hong、Peter Tontonoz、菅波孝祥
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cholesterol accumulation in CD11c+ immune cells is a causal and targetable factor in autoimmune disease2018

    • Author(s)
      Ito A, Hong C, Oka K, Salazar JV, Diehl C, Witztum JL, Diaz M, Castrillo A, Bensinger SJ, Chan L, Tontonoz P
    • Organizer
      Cell Symposia 'Translational Immunometabolism'
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脂質代謝と免疫応答のクロストーク2018

    • Author(s)
      伊藤綾香、Cynthia Hong、Peter Tontonoz、菅波孝祥
    • Organizer
      第36回内分泌代謝学サマーセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Molecular crosstalk between cholesterol metabolism and immune responses2018

    • Author(s)
      Ito A
    • Organizer
      The 4th IMCR Symposium on endocrine and metabolism
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cholesterol accumulation in CD11c+ immune cells is a causal and targetable factor in autoimmune disease2018

    • Author(s)
      Ito A, Hong C, Oka K, Salazar JV, Diehl C, Witztum JL, Diaz M, Castrillo A, Bensinger SJ, Chan L, Tontonoz P
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 自己免疫疾患発症における細胞内脂質代謝の意義2017

    • Author(s)
      伊藤綾香
    • Organizer
      第10回 Symphony
    • Related Report
      2017 Research-status Report
  • [Book] 実験医学増「脂質クオリティ」2018

    • Author(s)
      菅波孝祥、田中都、伊藤綾香、小川佳宏
    • Total Pages
      6
    • Publisher
      羊土社
    • ISBN
      9784758103718
    • Related Report
      2018 Annual Research Report
  • [Book] 医学のあゆみ2018

    • Author(s)
      伊藤綾香、菅波孝祥
    • Total Pages
      5
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2017 Research-status Report
  • [Remarks] 名古屋大学環境医学研究所分子代謝医学分野

    • URL

      http://www.riem.nagoya-u.ac.jp/4/mmm/index.html

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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