Development of CGRP-gene-transfected immune regulatory cells for treatment of refractory uveoretinitis in human

• Project/Area Number: 19592041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Tokyo Medical University
• Principal Investigator: KEZUKA Takeshi Tokyo Medical University, 医学部, 講師 (00287137)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Masaru 東京医科大学, 医学部, 准教授 (40260939)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: CGRP / 遺伝子導入細胞 / 難治性ぶどう膜炎 / 制御性細胞 / 神経ペプチド / 難治性視神経炎 / ぶどう膜炎 / 遺伝子治療 / 樹状細胞

Research Abstract

難治性ぶどう膜炎患者由来樹状細胞を用いた神経ペプチド (CGRP) 遺伝子の導入と、その免疫学的解析を行った。健常者の単核球同様、CGRP 遺伝子導入細胞からのCGRP 産生は40-60pg/mlであった。難治性ぶどう膜炎を持つベーチェット病患者から得られたCGRP 遺伝子導入細胞由来の培養上清中サイトカインは、対照群と比べて有意差を見いだせなかった。CGRP 刺激樹状細胞表面分子で免疫調節に関与する接着分子を検討したが、有意な結果が得られなかった。これらのことから、正常細胞を用いたCGRP 遺伝子導入実験では、制御性細胞を作成できるが、ベーチェット病患者由来の細胞では免疫制御細胞を誘導しなかった。今後、他の難治性ぶどう膜炎でも同様に検討する必要がある。

Research Products

• [Journal Article] Angiotensin II type 1 receptor blocker telmisartan suppresses experimental autoimmune uveitis (2009)
  • Author(s): Okunuki Y, Usui Y, Nagai N, Kezuka T, Ishida S, Takeuchi M, Goto H
  • Journal Title: Invest Ophthalmol Vis Sci (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 (2009)
  • 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 50 Pages: 263-72
  • 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. (2009)
  • Author(s): Sugita S
  • Journal Title: Invest Ophthalmol Vis Sci. 50 Pages: 263-272
  • 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] Increased levels of monokine induced by interferon-gamma (Mig) in the vitreous of patients with diabetic retinopathy (2008)
  • Author(s): Wakabayashi Y, Usui Y, Okunuki Y, Takeuchi M, Kezuka T, Iwasaki T, Goto H
  • Journal Title: Diabet Med 25 Pages: 875-7
  • 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: 1094-104
  • 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] Circulating neutrophils in Behcet disease is resistant for apoptotic cell death in the remission phase of uveitis (2008)
  • Author(s): Fujimori K, Oh-i K, Takeuchi M, Yamakawa N, Hattori T, Kezuka T, Keino H, Suzuki J, Goto H, Sakai J, Usui M
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 246 Pages: 285-90
  • Peer Reviewed
• [Journal Article] Functional expression of B7H1 on retinal pigment epithelial cells (2008)
  • Author(s): Usui, Y
  • Journal Title: Experimental Eye Research 82 Pages: 52-59
  • Peer Reviewed
• [Journal Article] Circulating neutrophils in Behcet disease is resistant for apoptotic cell death in the remission phase of uveitis (2008)
  • Author(s): Fujimori, K
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. 246 Pages: 285-290
  • Peer Reviewed
• [Journal Article] Proteomic surveillance of retinal autoantigens in endogenous uveitis : implication of esterase D and brain-type creatine kinase asnovel autoantigens (2008)
  • Author(s): Okunuki, Y
  • Journal Title: Molecular Vision 14 Pages: 1094-1104
  • Peer Reviewed
• [Journal Article] Increased levels of monokine induced by interferon-gamma (Mig) in the vitreous of patients with diabetic retinopathy. (2008)
  • Author(s): Wakabayashi Y
  • Journal Title: Diabet Med. 25 Pages: 875-877
  • 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
• [Presentation] ラット胎児胸腺移植ヌードマウスを用いた自己免疫生ぶどう膜炎の発症メカニズムの解析 (2008)
  • Author(s): 竹内大、服部貴明、臼井嘉彦、奥貫陽子、馬娟、山川直之、張リナ、毛塚剛司、後藤浩、田口修
  • Organizer: 第112回日本眼科学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-17
• [Presentation] Gene therapy with calcitonin gene-related peptide suppresses murine experimental autoimmune uveoretinitis (2008)
  • Author(s): Kezuka, T. et al
  • Organizer: ARVO 2008
• [Presentation] The mechanisms by which spontaneous development of organ-localized autoimmune diseases induced by xenogenic thymus (2008)
  • Author(s): Takeuchi M, Hattori T, Usui Y, Okunuki Y, Ma J, Yamakawa N, Zhang T, Kezuka T, Goto H, Taguchi O
  • Organizer: ARVO 2008
• [Presentation] Gene therapy with calcitonin gene-related peptide suppresses murine experimental autoimmune uveoretinitis. (2008)
  • Author(s): Kezuka, T., et al.
  • Organizer: ARVO 2008
  • Place of Presentation: 米国 フロリダ
• [Presentation] The mechanisms by which spontaneous development of organ-localized autoimmune diseases induced by xenogenic thymus. (2008)
  • Author(s): Takeuchi M
  • Organizer: ARVO2008
  • Place of Presentation: Florida U. S. A
• [Book] Acute retinal necrosis(92, Review) (2007)
  • Author(s): Kezuka T, Atherton SS
  • Publisher: Chem Immunol Allergy