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2010 Fiscal Year Final Research Report

Role of Immune co-signals in the pathogenesis and development of new treatment of refractory uveoretinitis

Research Project

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Project/Area Number 21791715
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionTokyo Medical University

Principal Investigator

USUI Yoshihiko  Tokyo Medical University, 医学部, 助教 (50408142)

Project Period (FY) 2009 – 2010
Keywordsぶどう膜網膜炎 / 補助シグナル分子 / CD4T細胞 / Th1反応 / Th17反応 / 眼ベーチェット / ICOS / サイトカイン
Research Abstract

Endogenous uveitis such as Behcet's disease (BD) is a potentially blinding disease in humans and is responsible for 10-15% of the acquired blindness in Japan. Although endogenous uveitis covers a spectrum of clinical entities, all forms are believed to share immunohistological similarities characterized by the infiltration of mainly CD4 T cells. It is well known that CD4 T cell activation requires the integration of at least two distinct signals. Signal one results from antigen-specific T cell receptor engagement by MHC class 2-bound peptide presented by antigen presenting cells (APC). Signal two results from engagement of costimulatory molecules expressed by APC and T cell. The CD28 homolog inducible costimulator (ICOS) has recently been identified as a novel member of the CD28 costimulator family, and is expressed by activated T cells in both humans and mice. The ICOS ligand, B7-related protein (B7RP-1), also known as B7 homologous protein (B7h), is constitutively expressed by APC. As the result of microarray analysis, ICOS in PBMCs showed the greatest difference in expression in BD patients with uveitis compared to healthy controls. ICOS expression on CD4 T cells in BD patients with uveitis was significantly higher than that in healthy individuals both before and after Con A stimulation. Among BD patients, ICOS expression on CD4 T cells was significantly higher in those with active uveitis than in those with remitted uveitis. Blockade of ICOS/B7-related protein-1 interaction by anti-ICOS mAb significantly decreased IFN-γ and IL-17 production by PBMCs when stimulated with Con A or IRBP in BD with active uveitis. In conclusion, our data provide additional evidence for the potential utility of ICOS expression on CD4 T cells as a marker to determine disease activity and that ICOS represents a promising therapeutic target for ocular BD by inhibiting Th1 and Th17 cytokines.

  • Research Products

    (26 results)

All 2010 2009 Other

All Journal Article (21 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Expression and function of inducible costimulator on peripheral blood CD4^+ T cells in Behcet's patients with uveitis : a new activity marker?2010

    • Author(s)
      Usui Y, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci 51

      Pages: 5099-5104

  • [Journal Article] Corrlation between cerebrospinal fluid cell count and cerebrospinal fluid level of chemokine, monokine induced by interferon-gamma in Vogt-Koyanagi-Harada disease.2010

    • Author(s)
      Keino H, Usui Y, et al.
    • Journal Title

      Acta Ophthalmol 88

      Pages: e30-31

  • [Journal Article] Functional and morphological changes in the eyes of Behcet's patients with uveitis.2010

    • Author(s)
      Takeuchi M, Iwasaki T, Kezuka T, Usui Y, et al.
    • Journal Title

      Acta Ophthalmol 88

      Pages: 257-262

  • [Journal Article] Suppression of bystander T helper 1 cells by iris pigment epithelium-inducing regulatory T cells via negative costimulatory signals.2010

    • Author(s)
      Sugita S, Horie S, Yamada Y, Keino H, Usui Y, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci 51

      Pages: 2529-2536

  • [Journal Article] Correlation of vascular endothelial growth factor with chemokines in the vitreous in diabetic retinopathy.2010

    • Author(s)
      Usui Y, Wakabayashi Y, et al.
    • Journal Title

      Retina 30

      Pages: 339-344

  • [Journal Article] Immune responses to interphotoreceptor retinoid-binding protein and S-antigen in Behcet's patients with uveitis.2010

    • Author(s)
      Takeuchi M, Usui Y, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci 51

      Pages: 3067-3075

  • [Journal Article] Clinical statistic of endogenous uveitis : comparison between general clinic and university hospital.2010

    • Author(s)
      Usui Y, et al.
    • Journal Title

      Int Ophthalmol 30

      Pages: 297-301

  • [Journal Article] Activation of aryl hydrocarbon receptor suppress experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells.2010

    • Author(s)
      Zhang L, Ma J, Takeuchi M, Usui Y, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci 51

      Pages: 2109-2117

  • [Journal Article] Increased levels of 8-hydroxydeoxyguanosine in the vitreous of patients with diabetic retinopathy.2010

    • Author(s)
      Usui Y, Wakabayashi Y, et al.
    • Journal Title

      Diabetes Res Clin Pract 89

      Pages: e59-61

  • [Journal Article] Human uveal melanoma cells inhibit the immunostimulatory function of dendritic cells.2010

    • Author(s)
      Usui Y, et al.
    • Journal Title

      Exp Eye Res 91

      Pages: 491-499

  • [Journal Article] Regulatory dendritic cell suppress experimental autoimmune uveoretinitis in mice.2009

    • Author(s)
      Usui Y, et al
    • Journal Title

      Arch Ophthalmol 127

      Pages: 514-519

  • [Journal Article] Angiotensin II type 1 receptor blocker telmisartan suppress experimental autoimmune uveitis.2009

    • Author(s)
      Usui Y, Okunuki Y, Nagai N, Kezuka T, Ishida S, Takeuchi M, et al
    • Journal Title

      Invest Ophthalmol Vis Sci 50

      Pages: 2255-2261

  • [Journal Article] T cell suppression by programmed cell death 1 ligand 1 on retinal pigment epithelium during inflammatory conditions.2009

    • Author(s)
      Sugita S, Usui Y, Horie S, Futagami Y, Aburatani H, Okazaki T, et al
    • Journal Title

      Invest Ophthalmol Vis Sci 50

      Pages: 2862-2870

  • [Journal Article] Dioxin promotes vascular endothelial growth factor (VEGF) production in the retina and enhances choroidal neovascularization.2009

    • Author(s)
      Takeuchi A, Takeuchi M, Oikawa K, Sonoda KH, Usui Y, Yoshida K, et al
    • Journal Title

      Invest Ophthalmol Vis Sci 50

      Pages: 3410-3416

  • [Journal Article] Presumed Vogt-Koyanagi-Harada Disease with unilateral ocular involvement : report of three cases.2009

    • Author(s)
      Usui Y, Goto H, Sakai J, Takeuchi M, Usui M, Rao NA
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol 247

      Pages: 1127-1132

  • [Journal Article] Human corneal endothelial cells expressing programmed death-ligand 1 (PD-L1) suppress PD-1+ T helper 1 cells by a contact-dependent mechanism.2009

    • Author(s)
      Sugita S, Usui Y, Horie S, Futagami Y, Yamada Y, Ma J, et al
    • Journal Title

      Invest Ophthalmol Vis Sci 50

      Pages: 263-272

  • [Journal Article] Human iris pigment epithelial cells suppress T-cell activation via direct cell contact.2009

    • Author(s)
      Hattori T, Kezuka T, Usui Y, Okunuki Y, Takeuchi M, Maruyama K, et al.
    • Journal Title

      Exp Eye Res 89

      Pages: 358-364

  • [Journal Article] Analysis of the pathogenesis of experimental autoimmune optic neuritis.

    • Author(s)
      Kezuka T, Usui Y, Goto H.
    • Journal Title

      J Biomed Biotechnol in press

  • [Journal Article] Four Cases of Delayed Onset Bilateral Acute Retinal Necrosis (ARN) in which Causative Virus in Both Eyes were Identified : an analysis of 108 cases of ARN.

    • Author(s)
      Okunuki Y, Usui Y, et al.
    • Journal Title

      Br J Ophthalmol. in press

  • [Journal Article] Arch of corneal opacity.

    • Author(s)
      Miyake T, Usui Y, Goto H.
    • Journal Title

      Arch Ophthalmol in press

  • [Journal Article] Relation of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy in branch retinal vein occlusion.

    • Author(s)
      Okunuki Y, Usui Y, et al.
    • Journal Title

      Am J Ophthalmol in press

  • [Presentation] Expression and Function of Inducible Costimulator in Patients with Ocular Behcet's Disease : Possible Involvement in IFN and IL-17 Production.2010

    • Author(s)
      Usui Y, Takeuchi M, Okuniki Y, Takeuchi A, Kezuka T, Hattori T, Matsuda R, Akiba H, Goto H.
    • Organizer
      Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      Fort Lauderdale.
    • Year and Date
      20100502-20100506
  • [Presentation] Immune responses to Interphotoreceptor Retinoid-binding protein and S-Antigen in Behcet's patients with uveitis.2010

    • Author(s)
      Takeuchi M, Usui Y, et al.
    • Organizer
      Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      Fort Lauderdale.
    • Year and Date
      20100502-20100506
  • [Presentation] Cytokine analysis to estimate the disease activity in Vogt-Koyanagi-Harada disease patients.2010

    • Author(s)
      Okunuki Y, Usui Y, et al.
    • Organizer
      Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      Fort Lauderdale.
    • Year and Date
      20100502-20100506
  • [Presentation] Vogt-小柳-原田病患者の末梢血単核球IL-17産生とステロイド治療に対する反応の検討2010

    • Author(s)
      奥貫陽子、臼井嘉彦, 他
    • Organizer
      第114回日本眼科学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      20100415-20100418
  • [Remarks] ホームページ等

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Published: 2012-02-13   Modified: 2016-04-21  

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