The development of immunosuppressive strategy for regenerative corneal allograft survival

• Project/Area Number: 19592046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Meiji College of Oriental Medicine
• Principal Investigator: YAMADA Jun Meiji College of Oriental Medicine, 医学教育研究センター, 准教授 (80351352)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Th17免疫応答 / Th1 / Th2 / 角膜移植拒絶反応 / 主要組織適合抗原(MHC) / マイナー抗原 / 免疫特権

Research Abstract

角膜移植拒絶は主にTヘルパー1型T細胞(Th1)が誘導するため、臨床応用に向けたTh1制御方法を開発してきた。しかし、BALB/cマウスで有効であったTh1制御による拒絶抑制はB6マウスでは無効であったため、拒絶におけるTh1以外の免疫応答の関与を検討した。結果、Th1応答が欠如した状態では、Th17応答ではなく、Th2応答が主体となって拒絶が生じることがわかった。免疫学的拒絶制御を臨床応用する際にはB6マウスでの制御方法の開発が必須である。

Research Products

• [Journal Article] MHC-matched corneal allograft rejection in an IFN-gamma/IL-17-independent manner inC57BL/6 mice (2009)
  • Author(s): Yamada J, Hamuro J, Fukushima A, Ohteki T, Terai K, Iwakura Y, Yagita H, Kinoshita S
  • Journal Title: Invest Ophthalmol Vis Sci (in press)
  • Peer Reviewed
• [Journal Article] Comparison of efficacy of bromfenacsodium 0.1% ophthalmic solution andfluorometholone 0.02% ophthalmic suspension for the treatment ofallergic conjunctivitis (2009)
  • Author(s): Fujishima H, Fukagawa K, Takano Y, Tanaka M, Okamoto S, Miyazaki D, Yamada J, Fukushima A, Uchio E, Nakagawa Y
  • Journal Title: Journal of ocular pharmacology and therapeutics (in press)
  • Peer Reviewed
• [Journal Article] Participation of CD11b and F4/80 molecules in the conjunctival eosinophilia of experimental allergic conjunctivitis (2009)
  • Author(s): Fukushima A, Ishida W, Kajisako M, Sumi T, Yamada J, Tsuru E, Miyazaki J, Tominaga A, Yagita H
  • Journal Title: International Archives of Allergy and Immunology (in press)
  • Peer Reviewed
• [Journal Article] MHC-matched corneal allograft rejection in an IFN-gamma/IL-17-independent manner in C57BL/6 mice (2009)
  • Author(s): Yamada J, Hamuro J, Fukushima A, Ohteki T, Terai K, Iwakura Y, Yagita H, Kinoshita S
  • Journal Title: Invest Ophthalmol Vis Sci. (印刷中)
  • Peer Reviewed
• [Journal Article] Endogenous IL-17 does not play a significant role in the development of experimental murine allergic conjunctivitis (2008)
  • Author(s): Fukushima A, Sumi T, Ishida W, Yamada J, Iwakura Y, Ueno H
  • Journal Title: Int Arch Allergy Immunol 147 Pages: 206-212
  • Peer Reviewed
• [Journal Article] Endogenous IL-17 does not play a significant role in the development of experimental murine allergic conjunctivitis. (2008)
  • Author(s): Fukushima A, Sumi T, Ishida W, Yamada J, Iwakura Y, Ueno H
  • Journal Title: Int Arch Allergy Immunol. 147 Pages: 206-212
  • Peer Reviewed
• [Journal Article] Alleviation of seasonalallergic symptoms with superfine beta-1, 3-glucan : A randomized study (2007)
  • Author(s): Yamada J, Hamuro J, Hatanaka H, Hamabata K, Kinoshita S
  • Journal Title: J Allergy Clin Immunol 119 Pages: 1119-1126
  • Peer Reviewed
• [Journal Article] MHC semi-matching improves murinecorneal allograft survival underoxidative macrophage dominancy (2007)
  • Author(s): Yamada J, Hamuro J, Terai K, Kinoshita S
  • Journal Title: Transplantation 84 Pages: 899-907
  • Peer Reviewed
• [Journal Article] Alleviation of seasonal allergic symptoms with superfine beta-1,3-glucan:A ralldomized study (2007)
  • Author(s): Yamada J, Hamuro J, Hatanaka H, Hamabata K, Kinoshita S
  • Journal Title: J Allergy Clin Immunol 119(5) Pages: 1119-1126
  • Peer Reviewed
• [Journal Article] MHC semi-matching improves murine corneal allograft survival under oxidative macrophage dominancy (2007)
  • Author(s): Yamada J, Hamuro J, Terai K, Kinoshita S
  • Journal Title: Transplantation 84(7) Pages: 889-907
  • Peer Reviewed
• [Presentation] Development of a new method for the measurement of corneal rigidity (2009)
  • Author(s): Terai K, Yamada J, Kinoshita S
  • Organizer: 81th Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale. Florida. U.S.A
  • Year and Date: 2009-05-05
• [Presentation] The role of neutrophil mediated corneal allograft rejection in C57BL/6-IFN-gamma KO hosts (2009)
  • Author(s): Yamada J, Hamuro J, Ohteki T, Terai K, Kinoshita S
  • Organizer: 81th Annual meeting of the ARVO(Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale. Florida. U.S.A
  • Year and Date: 2009-05-04
• [Presentation] INF-γ非依存性の拒絶における、Th1/Th2/Th17ケモカイン発現の検討 (2009)
  • Author(s): 山田潤, 羽室淳爾, 樗木俊聡, 寺井和都, 木下茂
  • Organizer: 第33回角膜カンファレンス・第25回日本角膜移植学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-02-19
• [Presentation] INF-γ非依存性の拒絶における、Th1/Th2/Th17ケモカイン発現の検討 (2009)
  • Author(s): 山田潤, 羽室淳爾, 樗木俊聡, 寺井和都, 木下茂
  • Organizer: 第33回角膜カンファレンス
  • Place of Presentation: 大阪
  • Year and Date: 2009-02-19
• [Presentation] Corneal allograft rejection by an IFN-gamma-independent immune response (2008)
  • Author(s): Yamada J, Hamuro J, Fukushima A, Terai K, Ohteki T, Iwakura Y, Kinoshita S
  • Organizer: 80th Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale. Florida. U.S.A
  • Year and Date: 2008-04-30
• [Presentation] Corneal allograft rejection by an IFN-gamma-independent immune response (2008)
  • Author(s): Yamada J, Hamuro J, Fukushima A, Terai K, Ohteki T, Iwakura Y, Kinoshita S
  • Organizer: 80th Annual meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale. Florida. U.S.A.
  • Year and Date: 2008-04-30
• [Presentation] IL-12/IL-18非依存性の全層角膜移植拒絶反応の検討 (2008)
  • Author(s): 山田潤, 羽室淳爾, 寺井和都, 福島敦樹, 中西憲司, 安田好文, 樗木俊聡, 木下茂
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-18
• [Presentation] マイナー抗原に対するIFN-γ非依存性の全層角膜移植拒絶反応の検討 (2008)
  • Author(s): 山田潤, 羽室淳爾, 福島敦樹, 石田わか, 樗木俊聡, 寺井和都, 木下茂
  • Organizer: 第32回角膜カンファレンス・第24回日本角膜移植学会
  • Place of Presentation: 千葉
  • Year and Date: 2008-02-28
• [Presentation] IL-12/IL-18非依存性の全層角膜移植拒絶反応の検討 (2007)
  • Author(s): 山田潤, 羽室淳爾, 中西憲司, 安田好文, 樗木俊聡, 寺井和都, 木下茂
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] IL-12/1L-18非依存性の全層角膜移植拒絶反応の検討 (2007)
  • Author(s): 山田 潤, 羽室 淳爾, 中西 憲司, 安田 好文, 樗木 俊聡, 寺井 和都, 木下 茂
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] ドライアイにおける結膜上皮表層細胞のチオール酸化還元機能 (2007)
  • Author(s): 山田潤, 横井則彦, 羽室淳爾, 寺井和都, 木下茂
  • Organizer: 第61回臨床眼科学会
  • Place of Presentation: 京都
  • Year and Date: 2007-10-11
• [Presentation] 細胞内チオールレドックス状態の制御からみた眼加齢医学 (2007)
  • Author(s): 山田潤
  • Organizer: 第7回抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2007-07-21
• [Presentation] 細胞内チオールレドックス状態の制御からみた眼加齢医学 (2007)
  • Author(s): 山田 潤
  • Organizer: 第7回抗加齢医学回総会
  • Place of Presentation: 京都
  • Year and Date: 2007-07-21
• [Presentation] MHC semi-matching improves corneal allograft survival by local skewing of intracellular redox status in antigen presenting cells to an oxidative form (2007)
  • Author(s): Hamuro J, Yamada J, Kinoshita S
  • Organizer: 50th SOE (European Society of Ophthalmology)
  • Place of Presentation: Vienna. Austria
  • Year and Date: 2007-06-09
• [Presentation] The Role of TGF-beta and Activin Signals in Corneal Epithelium Wound Healing in Organ Culture Experiment (2007)
  • Author(s): Terai K, Saika S, Yamada J, Kinoshita S, Kao W
  • Organizer: 79th Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale. Florida. U.S.A
  • Year and Date: 2007-05-08
• [Presentation] IL-15 Plays an Important Role in the Induction of Experimental Autoimmune Uveoretinitis (2007)
  • Author(s): Yamada J, Hamuro J, Terai K, Mochida C, Endo K, Ohteki T, Kinoshita S
  • Organizer: 79th Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale. Florida. U.S.A
  • Year and Date: 2007-05-08
• [Presentation] IL-15 plays an important role in the induction of experimental autoimmune uveoretinitis (2007)
  • Author(s): Yamada J, Hamuro J, Terai K, Mochida C, Endo KOhteki T, Kinoshita S
  • Organizer: 79th Annual meeting of the ARVO(Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale.Florida.U.S.A.
  • Year and Date: 2007-05-08
• [Presentation] The role of TGF-beta and activin signals in corneal epithelium wound healing in organ culture experiment (2007)
  • Author(s): Terai K, Saika S, Yamada J, Kinoshita S, Kao W
  • Organizer: 79th Annual meeting of the ARVO(Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale.Florida.U.S.A.
  • Year and Date: 2007-05-08
• [Presentation] MHC semi-matching improves comeal allograft survival by localskewing of intracellular redox status in antigen presenting cells to an oxidative form (2007)
  • Author(s): Hamuro J, Yamada J, Kinoshita S
  • Organizer: 50th SOE(European Society of Ophthalmology)
  • Place of Presentation: Vienna.Austria