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

Development of novel therapeutics for autoimmune inner ear disorder by using new transgenic mouse model

Research Project

Project/Area Number 18H02952
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionKeio University

Principal Investigator

Ogawa Kaoru  慶應義塾大学, 医学部(信濃町), 教授 (00169179)

Co-Investigator(Kenkyū-buntansha) 三枝 智香  慶應義塾大学, 医学部(信濃町), 特任助教 (00280800)
神崎 晶  慶應義塾大学, 医学部(信濃町), 講師 (50286556)
藤岡 正人  慶應義塾大学, 医学部(信濃町), 講師 (70398626)
細谷 誠  慶應義塾大学, 医学部(信濃町), 助教 (30645445)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywords自己免疫 / 耳科学 / 難聴 / メニエール病 / 橋渡し研究
Outline of Final Research Achievements

The involvement of autoimmunity has long been proposed as one of the causes of inner ear hearing loss. We have generated a novel transgenic mouse model in which immune tolerance to the cochlear sensory epithelium is disrupted, and have investigated the immunological surveillance mechanism of T cells against the cochlear sensory epithelium. In the present study, we performed comprehensive gene expression analysis to clarify the molecular pathogenesis of this phenomenon. Evidences showed that while antigen presentation was occurred in the cochlea under T-cell surveillance in CD4+ T-cell autoimmunity, gene expression changes are most prominent in the endolymphatic sac and includes apoptosis related genes.

Academic Significance and Societal Importance of the Research Achievements

自己免疫性内耳炎・難聴は、臨床的にステロイド剤に効果があることや炎症反応関連バイオマーカーの上昇、HLA型のSNPと難聴の相関などを根拠に提唱されてきた古くも新しい疾患概念であるが、一連の既報は、内耳組織の抗体産生能や、自己抗原の同定、内耳ペプチド摂取リンパ球による難聴誘導など、内耳組織は必ずしも免疫系に隔絶されてはいないことを示す状況証拠の蓄積であった。
本研究により、個体遺伝子操作による本格的な免疫学モデルにより、自己免疫=免疫寛容の破綻と感音難聴の因果関係がprospectiveに直接証明され、蝸牛ー内リンパ嚢という免疫反応の「軸」が内リンパ嚢恒常性の破綻を引きおこすことが示唆された。

Report

(3 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (12 results)

All 2020 2019 2018 Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (2 results)

  • [Journal Article] 幹細胞生物学と霊長類モデルを用いた内耳性難聴の治療法開発2020

    • Author(s)
      藤岡 正人
    • Journal Title

      Otology Japan

      Volume: 30巻1号 Pages: 11-18

    • NAID

      130007890724

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 【耳鼻咽喉科における新生児・乳幼児・小児への投薬-update-】 耳鼻咽喉科疾患に対する薬物療法 急性難聴2018

    • Author(s)
      藤岡正人
    • Journal Title

      ENTONI

      Volume: 218 Pages: 109-113

    • Related Report
      2018 Annual Research Report
  • [Presentation] ”新しい治療”を創り出す:産学官の"現場"の若手たち2019

    • Author(s)
      藤岡正人・武内 俊樹・黑川 友哉 ・阿部 圭悟・長倉 晃
    • Organizer
      第29回日本耳科学会総会・学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 当科におけるアパタイト人工耳小骨を用いた内視鏡下アブミ骨手術症例の検討2019

    • Author(s)
      藤岡 正人
    • Organizer
      第29回日本耳科学会総会・学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 難聴治療の最前線:経耳内視鏡下耳科手術(TEES)と幹細胞医学を用いた感音難聴治療2018

    • Author(s)
      藤岡正人
    • Organizer
      千代田区耳鼻咽喉科医会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Highly Efficient, Well-reproducible Cochlear Organoids Derived from Human Induced Pluripotent Cells: A Candidate Method of the Drug Development for Spiral Ganglion Neuron2018

    • Author(s)
      Sho Kurihara,Masato Fujioka, Tomohiko Yoshida, Makoto Hosoya, Kaoru Ogawa, Hiromi Kojima
    • Organizer
      European Academy of Otology and Neurotology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 幹細胞生物学を応用した内耳性難聴治療法の開発研究2018

    • Author(s)
      藤岡正人
    • Organizer
      第28回日本耳科学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞の内耳病態研究への応用と未来への展望~その長所・短所と位置付け~2018

    • Author(s)
      細谷誠、藤岡正人、小川郁
    • Organizer
      第28回日本耳科学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 幹細胞生物学を応用した内耳性難聴の研究2018

    • Author(s)
      藤岡正人
    • Organizer
      ディレグラWebセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 【難聴をなおす-2020年版】感音難聴とiPS創薬2020

    • Author(s)
      藤岡正人、細谷誠
    • Total Pages
      128
    • Publisher
      JOHNS
    • ISBN
      9784885635274
    • Related Report
      2019 Annual Research Report
  • [Remarks] 慶應義塾大学医学部耳鼻咽喉科学教室研究紹介

    • Related Report
      2019 Annual Research Report
  • [Remarks] 慶應義塾大学医学部耳鼻咽喉科学教室研究紹介

    • Related Report
      2018 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi