Role of inhibitory co-signal pathway in murine and human uveitis

• Project/Area Number: 19791294
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Tokyo Medical University
• Principal Investigator: USUI Yoshihiko Tokyo Medical University, 医学部, 助教 (50408142)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: ぶどう膜炎 / 抑制性補助シグナル / T細胞 / Th1反応 / 網膜色素上皮細胞 / サイトカイン / B7H1 / PD-1 / 角膜内皮細胞 / 抑制性補助シグナル分子 / T 細胞 / Th1 反応

Research Abstract

難治性ぶどう膜炎において重要な役割を果たすT細胞上に発現するProgrammed death 1(PD-1)は抗原提示細胞上のB7H1とB7DC分子の受容体として免疫抑制系に働く。また、B7H1とB7DCは抗原提示細胞のみならず組織にも発現し末梢免疫寛容に関与していることが報告されている。今回の我々の研究で、実験的自己免疫性ぶどう膜炎の動物モデルにおいてPD-1/PDLの系が抑制的に働いている可能性が示され、病態が増悪すると考えられた。網膜色素上皮細胞は眼内の炎症局所においてB7H1を介して免疫調節作用を有することが示唆された。

Research Products

• [Journal Article] Human corneal endothelial cells expressing Programmed Death-Ligand 1 suppress PD-1+T helper 1 cells by a contact-dependent mechanism (2009)
  • Author(s): Sugita S, Usui Y, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci 50 Pages: 263-272
  • Peer Reviewed
• [Journal Article] T cell suppression by programmed cell death 1 ligand 1 on retinal pig ment epithelium during inflammatory conditions (2009)
  • Author(s): Sugita S, Usui Y, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci (In press)
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor blocker telmisartan suppress experimental autoimm une uveitis (2009)
  • Author(s): Usui Y, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci (In press)
  • Peer Reviewed
• [Journal Article] Corrlation between cerebrospinal fluid cell count and cerebrospinal fluid level of chemokine, monokine induced by interferon-gamma in Vogt-Koyanagi-Harada dise ase (2009)
  • Author(s): Keino H, Usui Y, et.al.
  • Journal Title: Acta Ophthalmol (In press)
  • Peer Reviewed
• [Journal Article] B7-H3 contributes to the development of pathogenic Th2 cells in a murine model of asthma. (2008)
  • Author(s): Nagashima O, Harada N, Usui Y, Yamazaki T, Yagita H, Okumura K, Takahashi K, Akiba H
  • Journal Title: J Immunol 181 Pages: 4062-71
  • Peer Reviewed
• [Journal Article] Overview and diagnosis of acute retinal necrosis syndrome. (2008)
  • Author(s): Usui Y, Goto H
  • Journal Title: Semin Ophthalmol 23 Pages: 275-83
  • Peer Reviewed
• [Journal Article] Increased monokine induced by interferon-γ (Mig) levels in vitreous of patients with diabetic retinopathy. (2008)
  • Author(s): Usui Y, Wakabayashi Y, Okunuki Y, Takeuchi M, Kezuka T, Iwasaki T, Goto H
  • Journal Title: Diabet Med 25 Pages: 875-7
  • Peer Reviewed
• [Journal Article] Acute retinal necrosis in Japan. (2008)
  • Author(s): Usui Y, Takeuchi M, Goto H, Mori H, Kezuka T, Sakai J, Usui M
  • Journal Title: Ophthalmology 115 Pages: 1632-3
  • Peer Reviewed
• [Journal Article] Proteomic surveillance of retinal autoantigens in endogenous uveitis:implication of esterase D and brain-type creatine kinase as novel autoantigens. (2008)
  • Author(s): Okunuki Y, Usui Y, Kezuka T, Hattori T,Masuko K, Nakamura H, Yudoh K, Goto H, Usui M, Nishioka K, Kato T, Takeuchi M
  • Journal Title: Mol Vis 14 Pages: 1094-1104
  • Peer Reviewed
• [Journal Article] Immunopathology of necrotizing scleritis. (2008)
  • Author(s): Usui Y, Parikh J, Goto H, Rao NA
  • Journal Title: Br J Ophthalmol 92 Pages: 417-9
  • Peer Reviewed
• [Journal Article] Functional expression of B7H1 on retinal pigment epithelial cells. (2008)
  • Author(s): Usui Y, Okunuki Y, Hattori T, Kezuka T, Keino H, Ebihara N, Sugita S, Usui M, Goto H, Takeuchi M
  • Journal Title: Exp Eye Res 86 Pages: 52-9
  • Peer Reviewed
• [Journal Article] Phenoxazine derivative, 2-amino-4, 4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one suppresses growth of human retinoblastoma cell line Y79 in vitro and in vivo. (2008)
  • Author(s): Kimura K, Usui Y, Hattori T, Yamakawa N, Goto H, Usui M, Okada S, Shirato K, Tomoda A
  • Journal Title: Oncol Rep 19 Pages: 3-10
  • Peer Reviewed
• [Journal Article] Suppression of alkali burn-induced corneal neovascularization by dendritic cell vaccination targeting VEGF receptor 2. (2008)
  • Author(s): Mochimaru H, Usui T, Yaguchi T, Nagahama Y, Hasegawa G, Usui Y, Shimmura S, Tsubota K, Amano S, Kawakami Y, Ishida S
  • Journal Title: Invest Ophthalmol Vis Sci 49 Pages: 2172-7
  • Peer Reviewed
• [Journal Article] Functional expression of B7H1 on retinal pigment epithelial cells (2008)
  • Author(s): Usui Y, et.al.
  • Journal Title: Exp Eye Res 86 Pages: 52-59
  • Peer Reviewed
• [Journal Article] B7-H3 contributes to the development of pathogenic Th2 cells in a muri ne model of asthma (2008)
  • Author(s): Nagashima O, Harada N, Usui Y, et.al.
  • Journal Title: J Immunol 181 Pages: 4062-71
  • Peer Reviewed
• [Journal Article] Overview and diagnosis of acute retinal necrosis syndrome. (2008)
  • Author(s): Usui Y, et.al.
  • Journal Title: Semin Ophthalmol 23 Pages: 275-83
  • Peer Reviewed
• [Journal Article] Increased monokine induced by interferon-y (Mig) levels in vitreous of patients with diabetic retinopathy (2008)
  • Author(s): Usui Y, et.al.
  • Journal Title: Diabet Med 25 Pages: 875-7
  • Peer Reviewed
• [Journal Article] Acute retinal necrosis in Japan (2008)
  • Author(s): Usui Y, et.al.
  • Journal Title: Ophthalmology 115 Pages: 1632-3
  • Peer Reviewed
• [Journal Article] Proteomic surveillance of retinal autoantigens in endogenous uveitis : implication of esterase D and brain-type creatine kinase as novel autoantigens (2008)
  • Author(s): Okunuki Y, Usui Y, et.al.
  • Journal Title: Mol Vis 14 Pages: 1094-1104
  • Peer Reviewed
• [Journal Article] Immunopathology of necrotizing scleritis (2008)
  • Author(s): Usui Y, et.al.
  • Journal Title: Br J Ophthalmol 92 Pages: 417-9
  • Peer Reviewed
• [Journal Article] Phenoxazine derivative, 2-amino-4, 4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxaz ine-3-one suppresses growth of human retinoblastoma cell line Y79 in vitro and in vivo (2008)
  • Author(s): Kimura K, Usui Y, et.al.
  • Journal Title: Oncol Rep 19 Pages: 3-10
  • Peer Reviewed
• [Journal Article] Suppression of alkali bum-induced corneal neovascularization by dendritic cell va ccination targeting VEGF receptor 2 (2008)
  • Author(s): Mochimaru H, Usui T, Yaguchi T, Nagahama Y, Hasegawa G, Usui Y, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci 49 Pages: 2172-7
  • Peer Reviewed
• [Journal Article] Functional expression of B7H1 on retinal pifment epithelial cells (2008)
  • Author(s): Usui, Y, et. al.
  • Journal Title: Exp Eye Res 86 Pages: 52-59
  • Peer Reviewed
• [Journal Article] Blockade of the OX40 ligand prolongs corneal allograft survival. (2007)
  • Author(s): Hattori T, Usui Y, Okunuki Y, Sonoda Y, Usui M, Takada R, Mizoguchi J, Yagita H, Okumura K, Akiba H, Takeuchi M
  • Journal Title: Eur J Immunol 37 Pages: 3597-604
  • Peer Reviewed
• [Journal Article] Suppression of choroidal neovascularization by dendritic cell vaccination targeting VEGFR2. (2007)
  • Author(s): Mochimaru H, Nagai N, Hasegawa G, Kudo-Sato C, Yaguchi T, Usui Y, Kurihara T, Koto T, Satofuka S, Shinoda H, Ozawa Y, Tsubota K, Kawakami Y, Ishida S
  • Journal Title: Invest Ophthalmol Vis Sci 48 Pages: 4795-801
  • Peer Reviewed
• [Journal Article] Proteomic surveillance of autoimmunity in Behcet's disease with uveitis : Selenium binding protein is a novel autoantigen in Behcet's disease. (2007)
  • Author(s): Okunuki Y, Usui Y, Takeuchi M, Kezuka T, Hattori T, Masuko K, Nakamura H, Yudoh K, Usui M, Nishioka K, Kato T
  • Journal Title: Exp Eye Res 84 Pages: 823-31
  • Peer Reviewed
• [Journal Article] Regulatory Dendritic Cell Suppress Experimental Autoimmune Uveoretinitis in Mice.
  • Author(s): Usui Y, Takeuchi M, Hattori T, Okunuki Y, Nagasawa K, Kezuka T, Okumura K, Yagita H, Akiba H, Goto H
  • Journal Title: Arch Ophthalmol (in press)
  • Peer Reviewed
• [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.
  • Author(s): Sugita S, Usui Y, Horie S, Futagami Y, Yamada Y, Ma J, Kezuka T, Hamada H, Usui T, Mochizuki M, Yamagami S
  • Journal Title: Invest Ophthalmol Vis Sci (in press)
  • Peer Reviewed
• [Journal Article] Corrlation between cerebrospinal fluid cell count and cerebrospinal fluid level of chemokine, monokine induced by interferon-gamma in Vogt-Koyanagi-Harada disease.
  • Author(s): Keino H, Usui Y, Oh-I K, Usui M, Goto H
  • Journal Title: Acta Ophthalmol (in press)
  • Peer Reviewed
• [Journal Article] Dioxin promotes vascular endothelial growth factor (VEGF) production in the retina and enhances choroidal neovascularization.
  • Author(s): Takeuchi A, Takeuchi M, Oikawa K, Sonoda KH, Usui Y, Yoshida K, Okunuki Y, Usui M, Goto H, Kuroda M
  • Journal Title: Invest Ophthalmol Vis Sci (in press)
  • Peer Reviewed
• [Journal Article] Immrnopathology of necrotizing scleritis.
  • Author(s): Usui, Y, et. al.
  • Journal Title: Br J Ophthalmol (In press)
  • Peer Reviewed
• [Presentation] 抑制性補助シグナル分子PD-1/PDLのマウス実験的ぶどう膜網膜炎における役割 (2008)
  • Author(s): 臼井 嘉彦, 他
  • Organizer: 第161回東京医科大学医学会総会
  • Year and Date: 2008-06-07
• [Presentation] 抑制性補助シグナル分子PD-1/PDLのマウス実験的ぶどう膜網膜炎における役割 (2008)
  • Author(s): 臼井嘉彦, 他
  • Organizer: 第161回東京医科大学医学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-07
• [Presentation] 実験的自己免疫性ぶどう膜網膜炎における抑制性補助シグナル分子PD-1/PDL経路の役割 (2008)
  • Author(s): 臼井 嘉彦, 他
  • Organizer: 第112回日本眼科学会総会
• [Presentation] 急性網膜壊死患者の前房水および硝子体液中におけるサイトカイン・ケモカインの検討 (2008)
  • Author(s): 臼井 嘉彦, 他
  • Organizer: 第45回日本眼感染症学会
• [Presentation] 硝子体手術を施行した急性網膜壊死(桐沢型ぶどう膜炎)52例の検討 (2008)
  • Author(s): 臼井 嘉彦, 他
  • Organizer: 第62回日本臨床眼科学会
• [Presentation] ヒトぶどう膜悪性黒色腫が樹状細胞に与える免疫学的な影響 (2008)
  • Author(s): 臼井 嘉彦, 他
  • Organizer: 第26回日本眼腫瘍研究会
• [Presentation] Roles of programmed death-1 (PD-1)/PD-1 ligands pathway in the development of murine experimental autoimmune uveoretinitis (EAU) (2008)
  • Author(s): Usui Y, et al.
  • Organizer: 第38回日本免疫学会総会
• [Presentation] The Role of Programmed Death-1 (PD-1)/PD-L Pathway in Regulation of Murine Experimental Autoimmune Uveoretinitis (EAU) (2008)
  • Author(s): Usui Y, et al.
  • Organizer: 2008 Annual Meeting of the Association for Reaserch in Vision and Ophthalmology (ARVO)
• [Presentation] Cytokine profiles in patients with acute retinal necrosis : A prognostic marker analysis (2008)
  • Author(s): Usui Y, et al.
  • Organizer: 2008 American Academy of Ophthalmology
• [Presentation] 実験的自己免疫性ぶどう膜網膜炎における抑制性補助シグナル分子PD-1/PDL経路の役割 (2008)
  • Author(s): 臼井嘉彦, 他
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: パシフイコ横浜
• [Presentation] 急性網膜壊死患者の前房水および硝子体液中におけるサイトカイン・ケモカインの検討 (2008)
  • Author(s): 臼井嘉彦, 他
  • Organizer: 第45回日本眼感染症学会
  • Place of Presentation: 福岡
• [Presentation] 硝子体手術を施行した急性網膜壊死(桐沢型ぶどう膜炎)52例の検討 (2008)
  • Author(s): 臼井嘉彦, 他
  • Organizer: 第62回日本臨床眼科学会
  • Place of Presentation: 東京
• [Presentation] ヒトぶどう膜悪性黒色腫が樹状細胞に与える免疫学的な影響 (2008)
  • Author(s): 臼井嘉彦, 他
  • Organizer: 第26回日本眼腫瘍研究会
  • Place of Presentation: 東京
• [Presentation] Roles of programmed death-1 (PD-1)/PD-1 ligands pathway in the development of murine experimental autoimmune uveoretinitis (EAU) (2008)
  • Author(s): Usui Y et.al.
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
• [Presentation] The Role of Programmed Death-1 (PD-1)/PD-L Pathway in Regulation of Murine Experimental Autoimmune Uveoretinitis (EAU) (2008)
  • Author(s): Usui Y et.al.
  • Organizer: 2008 Annual Meeting of the Association for Rease rch in Vision and Ophthalmology (ARVO)
  • Place of Presentation: フロリダ
• [Presentation] Cytokine profiles in patients with acute retinal necrosis : A prognostic marker analysis (2008)
  • Author(s): Usui Y, et.al.
  • Organizer: 2008 American Academy of Ophthalmology
  • Place of Presentation: アトランタ
• [Presentation] 角膜血管新生におけるCD40の役割 (2008)
  • Author(s): 服部貴明、臼井嘉彦, 他
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 制御性樹状細胞による実験的自己免疫性ぶどう膜綱膜炎の抑制 (2007)
  • Author(s): 臼井嘉彦, 他
  • Organizer: 第111回日本眼科学会
  • Place of Presentation: 大阪