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2013 Fiscal Year Final Research Report

Molecular mechanisms of immunosuppressive intraocular microenvironment in corneal transplantation

Research Project

  • PDF
Project/Area Number 23592619
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionNippon Medical School

Principal Investigator

HORI Junko  日本医科大学, 医学部, 准教授 (60251279)

Co-Investigator(Kenkyū-buntansha) KITAHARA Yuki  日本医科大学, 医学部, 助教 (30360176)
TANIGUCHI Hiroko  日本医科大学, 医学部, 研究員 (00535445)
Research Collaborator AZUMA Miyuki  東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (90255654)
YAGITA Hideo  順天堂大学, 医学部, 准教授 (30182306)
Project Period (FY) 2011 – 2013
Keywords免疫特権 / 副刺激シグナル / 移植免疫応答 / Galectin-9/Tim-3 / ICOS/B7RP-1(ICOSL)
Research Abstract

(1) Tim-3 is a regulatory molecule for T-cell function, and Gal-9 is a Tim-3 ligand. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 mAb or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Gal-9 may play an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.
(2) ICOS/B7RP-1 signaling has an immune suppressive effect in corneal allografts. B7RP-1 expressed on ocular tissue and ICOS expressed on T-cells may interact in the eye and play a role in the survival of the corneal allograft.

  • Research Products

    (32 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (24 results) Remarks (3 results)

  • [Journal Article] Galectin-9-mediated protection from allo-specific T cells as a mechanism of immune privilege of corneal allografts2013

    • Author(s)
      Shimmura-Tomita M, Wang M, Taniguchi H, Akiba H, Yagita H, Hori J
    • Journal Title

      PLoS One

      Volume: 8(5) Pages: e63620

    • DOI

      10.1371/journal.pone.0063620

    • Peer Reviewed
  • [Journal Article] Immune privilege as new therapeutic strategies for success of corneal transplantation2013

    • Author(s)
      Kunishige T, Hori J
    • Journal Title

      Journal of Inflammation and Regeneration

      Volume: 33(5)

    • URL

      http://jsir.gr.jp/journal/Vol33No5/pdf/0274-0282.pdf

    • Peer Reviewed
  • [Journal Article] 眼表面の免疫特権、「オキュラーサーフェス診療アップデート」2012

    • Author(s)
      国重智之、堀純子
    • Journal Title

      臨床眼科(医学書院)

      Volume: 66巻 Pages: 346-350

    • Peer Reviewed
  • [Journal Article] GITR ligand-mediated local expansion of regulatory T cells contributes to immune privilege of corneal allografts2010

    • Author(s)
      Hori J, Taniguchi H, Wang M, Oshima M, Azuma M
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 51(12) Pages: 6556-65

    • DOI

      10.1167/iovs.09-4959

    • Peer Reviewed
  • [Journal Article] Review of ocular immune privilege in the year 2010: modifying the immune privilege of the eye2010

    • Author(s)
      Hori J, Vega JL, Masli S
    • Journal Title

      Ocul Immunol Inflamm

      Volume: 18(5) Pages: 325-33

    • DOI

      10.3109/09273948.2010.512696

    • Peer Reviewed
  • [Presentation] Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) on Immune Privilege of Corneal Allograft2014

    • Author(s)
      T Kunishige, H Taniguchi, T Ohno, M Azuma, J Hori
    • Organizer
      WOC (World Ophthalmology Congress)
    • Place of Presentation
      東京
    • Year and Date
      20140400
  • [Presentation] Novel Developments in the Investigation of Ocular Immunomodulation「Anterior chamber-associated immune deviation (ACAID)」2014

    • Author(s)
      J Hori
    • Organizer
      第118回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-05
  • [Presentation] 角膜移植の生着におけるV-domain Ig Suppressor of T Cell Activation (VISTA)の役割2013

    • Author(s)
      國重智之、谷口ヒロ子、堀純子、大野建州、東みゆき
    • Organizer
      第47回日本眼炎症学会
    • Place of Presentation
      大阪
    • Year and Date
      2013-07-01
  • [Presentation] V-domain Ig Suppressor of T Cell Activation (VISTA) is Necessary for Corneal Allograft Survival2013

    • Author(s)
      T Kunishige, H Taniguchi, T Ohno, M Azuma, J Hori
    • Organizer
      ARVO (Association for research in vision and ophthalmology)
    • Place of Presentation
      Seattle
    • Year and Date
      2013-05-06
  • [Presentation] Induction of Corneal Inflammation in the Collagen-Induced Scleritis Model2013

    • Author(s)
      H Taniguchi, Y Kitahara, J Hori
    • Organizer
      ARVO (Association for research in vision and ophthalmology)
    • Place of Presentation
      Seattle
    • Year and Date
      2013-05-06
  • [Presentation] コラーゲン誘導性強膜炎モデルにおける角膜病変の誘導2013

    • Author(s)
      谷口ヒロ子、王明聡、北原由紀、中島敦夫、堀純子
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2013-04-06
  • [Presentation] 眼の恒常性の不思議"Immune privilege"の謎を解く—亡き恩師からのミッション—2012

    • Author(s)
      堀純子
    • Organizer
      宮城眼科先進医療研究会
    • Place of Presentation
      宮城
    • Year and Date
      2012-10-03
  • [Presentation] 眼炎症疾患へのアプローチー診断のコツと新治療の展望2012

    • Author(s)
      堀純子
    • Organizer
      函館眼科医会学術講演会
    • Place of Presentation
      北海道
    • Year and Date
      2012-08-27
  • [Presentation] 角膜移植後の免疫寛容におけるTim-3 / Gal-9経路の抑制的役割2012

    • Author(s)
      榛村真智子、堀純子、王明聡、谷口ヒロ子、高橋浩、梯彰弘、秋葉久弥、八木田秀雄
    • Organizer
      第46回日本眼炎症学会
    • Place of Presentation
      横浜
    • Year and Date
      2012-07-15
  • [Presentation] Inhibitory Role of ICOS in Antigen-specific T cell-mediated Ocular Tissue Damage2012

    • Author(s)
      M Terada, H Taniguchi, K Maruyama, R Abe, J Hori
    • Organizer
      ARVO
    • Place of Presentation
      USA
    • Year and Date
      2012-05-10
  • [Presentation] Ocular Immune Pathological Analysis in a Murine Model of Anterior Scleritis2012

    • Author(s)
      H Taniguchi, MC Wang, Y Kitahara, A Nakajima, J Hori
    • Organizer
      ARVO
    • Place of Presentation
      USA
    • Year and Date
      2012-05-10
  • [Presentation] 眼炎症を制御する新しい分子群Molecular mechanisms in regulation of ocular inflammation2012

    • Author(s)
      堀純子、谷口ヒロ子
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-06
  • [Presentation] 抗原特異的T細胞による眼組織障害におけるICOSの抑制的役割2012

    • Author(s)
      寺田節, 堀純子, 谷口ヒロ子, 安部良
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-05
  • [Presentation] 前部強膜炎マウスモデルにおける眼局所の病態解析2012

    • Author(s)
      谷口ヒロ子、堀純子、王明聡、北原由紀、中島敦夫
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-05
  • [Presentation] 眼炎症の自動制御機構"免疫特権"の謎を解く2011

    • Author(s)
      堀純子
    • Organizer
      レディースアイフォーラムin横浜
    • Place of Presentation
      神奈川
    • Year and Date
      20110800
  • [Presentation] 角膜移植の免疫特権におけるTim-3/Gal-9経路の役割2011

    • Author(s)
      榛村真智子、堀純子、王明聡、谷口ヒロ子、秋葉久弥、八木田秀雄
    • Organizer
      第16回Tokyo Ocular Immunology Meeting
    • Place of Presentation
      東京
    • Year and Date
      2011-09-30
  • [Presentation] 角膜アログラフトの生着における脾臓内Foxp3+CD8+制御性T細胞の関与2011

    • Author(s)
      谷口ヒロ子、堀純子、秋葉久弥、八木田秀雄、東みゆき
    • Organizer
      第45回日本眼炎症学会
    • Place of Presentation
      京都
    • Year and Date
      2011-07-09
  • [Presentation] Ocular cell-mediated regulation and immune privilege. ARVO/JOS symposium : Immune pathogenesis and regulation in the eye2011

    • Author(s)
      J Hori
    • Organizer
      第115回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-12
  • [Presentation] 角膜移植後の眼局所におけるTLT-2の発現と機能2011

    • Author(s)
      谷口ヒロ子、堀純子、秋葉久弥、八木田秀雄、長谷英徳、東みゆき
    • Organizer
      第115回日本眼科学会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-12
  • [Presentation] 角膜血管リンパ管新生における二次リンパ器官の関与とICOSの抑制的役割2011

    • Author(s)
      寺田節、堀純子、谷口ヒロ子、丸山和一、安部良
    • Organizer
      第115回日本眼科学会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-12
  • [Presentation] Expression of TLT-2 in corneal tissue and macrophages after corneal transplantation and association with immune privilege of corneal allografts2011

    • Author(s)
      H. Taniguchi, H. Sase, H. Akiba, H. Yagita, M. Azuma, J. Hori
    • Organizer
      ARVO
    • Place of Presentation
      USA
    • Year and Date
      2011-05-04
  • [Presentation] Correlation between proportion of splenic Foxp3+CD8+T regulatory cells and corneal allograft survival2011

    • Author(s)
      K. Wakayama, H. Taniguchi, H. Akiba, H. Yagita, M. Azuma, J. Hori
    • Organizer
      ARVO
    • Place of Presentation
      USA
    • Year and Date
      2011-05-01
  • [Presentation] Inhibitory role of ICOS on corneal lymphangiogenesis and involvement of Foxp3+CD4+T regulatory cells in secondary lymphoid organs2011

    • Author(s)
      M. Terada, H. Taniguchi, K. Maruyama, R. Abe, J. Hori
    • Organizer
      ARVO
    • Place of Presentation
      USA
    • Year and Date
      2011-05-01
  • [Presentation] 眼の恒常性の不思議"Immune privilege"の謎を解く2011

    • Author(s)
      堀純子
    • Organizer
      第3回学問のすすめ
    • Place of Presentation
      新潟
    • Year and Date
      2011-04-02
  • [Remarks] 研究テーマおよび研究内容

    • URL

      http://tlo.nms.ac.jp/researcher/1193.html

  • [Remarks] 研究テーマおよび研究内容

    • URL

      http://hosp.nms.ac.jp/staff/988.html

  • [Remarks] 日本医科大学眼科研究業績

    • URL

      http://www.nms.ac.jp/nms/ganka/achievements/original.html

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Published: 2015-07-16  

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