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Multiomics analysis of auto reactive immune cells in the inflammatory sites in autoimmune diseases.

Research Project

Project/Area Number 17H04216
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionKeio University

Principal Investigator

Takeuchi Tsutomu  慶應義塾大学, 医学部(信濃町), 教授 (50179610)

Co-Investigator(Kenkyū-buntansha) 竹下 勝  慶應義塾大学, 医学部(信濃町), 特任助教 (10571135)
鈴木 勝也  慶應義塾大学, 医学部(信濃町), 講師 (70306695)
浅川 修一  東京大学, 大学院農学生命科学研究科(農学部), 教授 (30231872)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords自己免疫 / シェーグレン症候群 / B細胞 / 抗セントロメア抗体 / 自己抗原 / 自己抗体 / 全身性強皮症 / レパトア解析 / 自己免疫疾患
Outline of Final Research Achievements

It is known that lymphocytes (B cells, T cells) that react to self-protein are present in patients with autoimmune disease, but the dynamics of these cells at the lesion site was not clear. In this study, we focused on the cells in the local lesions of Sjogren's syndrome (saliva glands) and analyzed what they responded to, especially B cells. We clarified that one third of B cells at the lesion site produced antibodies against self-protein, and these cells were specifically selected for the self-antigen at the lesion site. These results about origin of autoantibodies in the local lesion is considered to be an important clue to reveal disease pathophysiology.

Academic Significance and Societal Importance of the Research Achievements

本研究により、B細胞の自己反応性を病変部位で確認できる事が明らかになり、自己免疫反応がなぜ起こるのか、という根本的な病態解明に向けて、病変部位の解析の重要性が示された。また、病変部位の探索により新規の自己抗原を同定できることも明らかになった。同様の手法は他の自己免疫疾患の組織にも応用可能であり、本研究は今後の自己免疫疾患の研究におけるモデルケースになると考えられた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (7 results)

All 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Antigen-driven selection of antibodies against SSA, SSB and the centromere ‘complex’, including a novel antigen, MIS12 complex, in human salivary glands2019

    • Author(s)
      Takeshita Masaru、Suzuki Katsuya、Kaneda Yukari、Yamane Humitsugu、Ikeura Kazuhiro、Sato Hidekazu、Kato Shin、Tsunoda Kazuyuki、Arase Hisashi、Takeuchi Tsutomu
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 79 Issue: 1 Pages: 150-158

    • DOI

      10.1136/annrheumdis-2019-215862

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Initial presenting determines clinical entity in patients with anti-centromere antibody positivity.2018

    • Author(s)
      Tsukamoto M, Suzuki K, and Takeuchi T.
    • Journal Title

      Int J Rheum Dis

      Volume: ー

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and immunological features of anti-centromere antibody-positive sjogren’s syndrome.2018

    • Author(s)
      Tsukamoto M, Suzuki K, and Takeuchi T
    • Journal Title

      Rheumatol Ther,

      Volume: 5 Pages: 499-505

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Reactivity of antibodies in the salivary glands of Sjögren's syndrome reveals affinity maturation in disease lesion and the significance of anti-centromere “complex” antibody in disease classification.2019

    • Author(s)
      Masaru Takeshita, Katsuya Suzuki, Tsutomu Takeuchi.
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] シェーグレン症候群の病変局所における自己抗体産生から明らかになった抗セントロメア抗体の疾患分類上の意義について2019

    • Author(s)
      竹下 勝、鈴木 勝也、金田 由加梨、山根 史嗣、池浦 一裕、佐藤 秀和、加藤 伸、角田 和之、荒瀬 尚、竹内 勤
    • Organizer
      第6回JCRベーシックリサーチカンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] シェーグレン症候群の唾液腺における自己抗体産生2018

    • Author(s)
      竹下 勝、鈴木 勝也、竹内 勤
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 自己免疫疾患の検出剤となるタンパク質複合体、及びその使用2019

    • Inventor(s)
      竹下 勝、竹内 勤、鈴木 勝也
    • Industrial Property Rights Holder
      竹下 勝、竹内 勤、鈴木 勝也
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-107179
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-12-28  

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