Functional analysis of costimulatory molecules in autoimmune uveitis and their intervention for clinical application

• Project/Area Number: 19592040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Juntendo University
• Principal Investigator: AKIBA Hisaya Juntendo University, 医学部, 准教授 (60338316)
• Co-Investigator(Kenkyū-buntansha): USUI Yoshihiko 東京医科大学, 医学部, 助教 (50408142)
• 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: T細胞分化・制御 / 補助シグナル分子 / 自己免疫疾患 / 喘息 / アレルギー / 実験的自己免疫性ぶどう膜網膜炎 / EAU / OX40-OX40L

Research Abstract

補助シグナル分子は、T細胞の活性化や機能に重要な役割を担っており、これらの働きを制御する抗体を開発することにより、難治性ぶどう膜網膜炎の治療が可能になるのではないかと考え、種々の補助シグナル分子に対する抗体を作製し、ぶどう膜網膜炎マウスモデルに投与して治癒効果の検討を行った。この内、T細胞分化に関わる補助シグナル分子OX40Lに対する抗体投与が、発症抑制に効果的であり、臨床応用に期待がもてる結果が得られた。

Research Products

• [Journal Article] Suppression of experimental autoimmune uveoretinitis by regulatory dendritic cells in mice (2009)
  • Author(s): Usui, Y., M. Takeuchi, T. Hattori, Y. Okunuki, K. Nagasawa, T. Kezuka, K. Okumura, H. Yagita, H. Akiba, and H. Goto.
  • Journal Title: Arch Ophthalmol 127 Pages: 514-519
  • Peer Reviewed
• [Journal Article] RANK-RANKL signaling pathway is critically involved in the function of CD4+ CD25+ regulatory T cells in chronic colitis (2009)
  • Author(s): Totsuka, T., T. Kanai, Y. Nemoto, T. Tomita, R. Okamoto, K. Tsuchiya, T. Nakamura, N. Sakamoto, H. Akiba, K. Okumura, H. Yagita, and M. Watanabe.
  • Journal Title: J Immunol 182 Pages: 6079-6087
  • Peer Reviewed
• [Journal Article] Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation (2009)
  • Author(s): Nakayama, M., H. Akiba, K. Takeda, Y. Kojima, M. Hashiguchi, M. Azuma, H. Yagita, and K. Okumura
  • Journal Title: Blood 113 Pages: 3821-3830
  • Peer Reviewed
• [Journal Article] Notch signaling confers antigen-presenting cell functions on mast cells (2009)
  • Author(s): Nakano, N., C. Nishiyama, H. Yagita, A. Koyanagi, H. Akiba, S. Chiba, H. Ogawa, and K. Okumura
  • Journal Title: J Allergy Clin Immunol 123 Pages: 74-81
  • Peer Reviewed
• [Journal Article] Notch signaling confers antigen-presenting cell functions on mast cells. (2009)
  • Author(s): Nakano N
  • Journal Title: J Allergy Clin Immunol 123 Pages: 74-81
  • Peer Reviewed
• [Journal Article] Peritubular ischemia contributes more to tubular damage than proteinuria in immune-mediated glomerulonephritis (2008)
  • Author(s): Wong, M. G., Y. Suzuki, C. Tanifuji, H. Akiba, K. Okumura, T. Sugaya, T. Yamamoto, S. Horikoshi, S. Y. Tan, C. Pollock, and Y. Tomino.
  • Journal Title: J Am Soc Nephrol 19 Pages: 290-297
  • Peer Reviewed
• [Journal Article] The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant model (2008)
  • Author(s): Ueno, T., A. Habicht, M. R. Clarkson, M. J. Albin, K. Yamaura, O. Boenisch, J. Popoola, Y. Wang, H. Yagita, H. Akiba, M. J. Ansari, J. Yang, L. A. Turka, D. M. Rothstein, R. F. Padera, N. Najafian, and M. H. Sayegh
  • Journal Title: J Clin Invest 118 Pages: 742-751
  • 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., N. Harada, Y. Usui, T. Yamazaki, H. Yagita, K. Okumura, K. Takahashi, and H. Akiba
  • Journal Title: J Immunol 181 Pages: 4062-4071
  • Peer Reviewed
• [Journal Article] Roles of galectin-9 in the development of experimental allergic conjunctivitis in mice (2008)
  • Author(s): Fukushima, A., T. Sumi, K. Fukuda, N. Kumagai, T. Nishida, K. Okumura, H. Akiba, H. Yagita, and H. Ueno.
  • Journal Title: Int Arch Allergy Immunol 146 Pages: 36-43
  • Peer Reviewed
• [Journal Article] A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine (2008)
  • Author(s): Chen, Q., J. L. Cannons, J. C. Paton, H. Akiba, P. L. Schwartzberg, and C. M. Snapper
  • Journal Title: J Immunol 181 Pages: 8258-8266
  • Peer Reviewed
• [Journal Article] A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine. (2008)
  • Author(s): Chen Q
  • Journal Title: J Immunol 181 Pages: 8258-66
  • 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
  • Journal Title: J Immunol 181 Pages: 4062-71
  • Peer Reviewed
• [Journal Article] The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant model. (2008)
  • Author(s): Ueno T
  • Journal Title: J Clin Invest 118 Pages: 742-51
  • Peer Reviewed
• [Journal Article] Peritubular ischemia contributes more to tubular damage than proteinuria in immune-mediated glomerulonephritis. (2008)
  • Author(s): Wong MG
  • Journal Title: J Am Soc Nephrol 19 Pages: 290-7
  • Peer Reviewed
• [Journal Article] Roles of galectin-9 in the development of experimental allergic conjunctivitis in mice. (2008)
  • Author(s): Fukushima A
  • Journal Title: Int Arch Allergy Immunol 146 Pages: 36-43
  • Peer Reviewed
• [Journal Article] The emerging role of T cell Ig mucin 1 in alloimmune responses in an experimental mouse transplant model (2008)
  • Author(s): Ueno T
  • Journal Title: J Clin Invest 118 Pages: 742-751
  • Peer Reviewed
• [Journal Article] Peritubular ischemia contributes more to tubular damage than proteinuria in immune-mediated glomerulonephritis (2008)
  • Author(s): Wong MG
  • Journal Title: J Am Soc Nephrol 19 Pages: 290-297
  • Peer Reviewed
• [Journal Article] Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function (2007)
  • Author(s): Xiao, S., N. Najafian, J. Reddy, M. Albin, C. Zhu, E. Jensen, J. Imitola, T. Korn, A. C. Anderson, Z. Zhang, C. Gutierrez, T. Moll, R. A. Sobel, D. T. Umetsu, H. Yagita, H. Akiba, T. Strom, M. H. Sayegh, R. H. DeKruyff, S. J. Khoury, and V. K. Kuchroo
  • Journal Title: J Exp Med 204 Pages: 1691-1702
  • Peer Reviewed
• [Journal Article] TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells (2007)
  • Author(s): Nakae, S., M. Iikura, H. Suto, H. Akiba, D. T. Umetsu, R. H. Dekruyff, H. Saito, and S. J. Galli
  • Journal Title: Blood 110 Pages: 2565-2568
  • Peer Reviewed
• [Journal Article] Blockade of the OX40 ligand prolongs corneal allograft survival (2007)
  • Author(s): Hattori, T., Y. Usui, Y. Okunuki, Y. Sonoda, M. Usui, E. Takada, J. Mizuguchi, H. Yagita, K. Okumura, H. Akiba, and M. Takeuchi
  • Journal Title: Eur J Immunol 37 Pages: 3597-3604
  • Peer Reviewed
• [Journal Article] B7-H3 regulates the development of experimental allergic conjunctivitis in mice (2007)
  • Author(s): Fukushima, A., T. Sumi, K. Fukuda, N. Kumagai, T. Nishida, T. Yamazaki, H. Akiba, K. Okumura, H. Yagita, and H. Ueno
  • Journal Title: Immunol Lett 113 Pages: 52-57
  • Peer Reviewed
• [Journal Article] T-cell Ig and mucin domain-containing protein (Tim)-2 regulates murine allergic conjunctivitis during the effector phase (2007)
  • Author(s): Fukushima, A., T. Sumi, K. Fukuda, N. Kumagai, T. Nishida, K. Okumura, H. Akiba, H. Yagita, and H. Ueno
  • Journal Title: Immunol Lett 110 Pages: 133-138
  • Peer Reviewed
• [Journal Article] Antibodies to T-cell Ig and mucin domain-containing proteins (Tim)-1 and -3 suppress the induction and progression of murine allergic conjunctivitis (2007)
  • Author(s): Fukushima, A., T. Sumi, K. Fukuda, N. Kumagai, T. Nishida, H. Akiba, K. Okumura, H. Yagita, and H. Ueno
  • Journal Title: Biochem Biophys Res Commun 353 Pages: 211-216
  • Peer Reviewed
• [Journal Article] Roles of Galectin-9 in the Development of Experimental Allergic Conjunctivitis in Mice (2007)
  • Author(s): Fukushima A
  • Journal Title: Int Arch Allergy Immunol 146 Pages: 36-43
  • Peer Reviewed
• [Journal Article] Blockade of the OX40 ligand prolongs corneal allograft survival (2007)
  • Author(s): Hattori T
  • Journal Title: Eur J Immunol 37 Pages: 3597-3604
  • Peer Reviewed
• [Journal Article] B7-H3 regulates the development of experimental allergic conjunctivitis in mice (2007)
  • Author(s): Fukushima A
  • Journal Title: Immunol Lett 113 Pages: 52-57
  • Peer Reviewed
• [Journal Article] TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells (2007)
  • Author(s): Nakae S
  • Journal Title: Blood 110 Pages: 2565-2568
  • Peer Reviewed
• [Journal Article] Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function (2007)
  • Author(s): Xiao S
  • Journal Title: J Exp Med 204 Pages: 1691-1702
  • Peer Reviewed
• [Journal Article] T-cell Ig and mucin domain-containing protein(Tim)-2 regulates murine allergic conjunctivitis during the effector phase (2007)
  • Author(s): Fukushima A
  • Journal Title: Immunol Lett 110 Pages: 133-138
  • Peer Reviewed
• [Journal Article] Antibodies to T-cell Ig and mucin domain-containing proteins(Tim)-1and-3suppress the induction and progression of murine allergic conjunctivitis (2007)
  • Author(s): Fukushima A
  • Journal Title: Biochem Biophys Res Commun 353 Pages: 211-216
  • Peer Reviewed
• [Presentation] TIM-3 mediates phagocytosis of apoptotic cells by inflammatory macrophage and CD8 dendritic cell subsets (2008)
  • Author(s): Nakayama M.
  • Organizer: 日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-03
• [Presentation] The role of TIM-2 in regulation of collagen-induced arthritis (2008)
  • Author(s): Kawamoto T.
  • Organizer: 日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-02
• [Presentation] Roles of PD-1/PD-1 ligands pathway in the development of murine experimental autoimmune uveoretinitis (2008)
  • Author(s): Usui Y.
  • Organizer: 日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-01
• [Presentation] Roles of PD-l/PD-1 ligands pathway in the development of murine experimenta1 autoimmune uveoretinitis. (2008)
  • Author(s): Usui Y
  • Organizer: 日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-01
• [Presentation] The role of PD-1/PD-L pathway in regulation of murine experimental autoimmune uveoretinitis (EAU). (2008)
  • Author(s): Usui Y
  • Organizer: The Association for Reseach in Vision and Ophthalmology, Annual Meeting 2008
  • Place of Presentation: Fort Lauderdale, FL
  • Year and Date: 2008-04-30
• [Presentation] Functional expression of CD40 in corneal neovasculization (2008)
  • Author(s): Hattori T.
  • Organizer: The Association for Reseach in Vision and Ophthalmology, Annual Meeting
  • Place of Presentation: Fort Lauderdale, FL
  • Year and Date: 2008-04-28
• [Presentation] Functional expression of CD40 in corneal neovasculization. (2008)
  • Author(s): Hattori T
  • Organizer: The Association for Reseach in Vision and Ophthalmology, Annual Meeting 2008
  • Place of Presentation: Fort Lauderdale, FL
  • Year and Date: 2008-04-28
• [Presentation] Notch signaling induces MHC class II expression on mast cell surface (2007)
  • Author(s): Nakano Nobuhiro
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-21
• [Presentation] TIM-1 signaling in B cells regulates antibody production (2007)
  • Author(s): Akiba H.
  • Organizer: 日本免疫学会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-20
• [Presentation] B7-H3 regulates asthmatic response in a murine model of asthma (2007)
  • Author(s): Nagashima O.
  • Organizer: 日本免疫学会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-20
• [Presentation] Notch signaling induces MHC class II expression on mast cell surface (2007)
  • Author(s): Nakano N.
  • Organizer: 日本免疫学会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-20
• [Presentation] TIM-1 signaling in B cells regulates antibody production (2007)
  • Author(s): Akiba Hisaya
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-20
• [Presentation] B7-H3 regulates asthmatic response in a murine model of asthma (2007)
  • Author(s): Nagashima Osamu
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-20
• [Presentation] 実験的アレルギー性結膜疾患発症における共刺激分子Tim の関与 (2007)
  • Author(s): Fukushima A.
  • Organizer: 日本眼炎症学会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2007-07-06
• [Presentation] 実験的アレルギー性結膜疾患発症における共刺激分子Timの関与 (2007)
  • Author(s): 福島 敦樹
  • Organizer: 第41回日本眼炎症学会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2007-07-06
• [Presentation] The role of PD-1/PD-L pathway in regulation of murine experimental autoimmune uveoretin-itis (EAU)
  • Author(s): Usui Y.
  • Organizer: The Association for Reseach in Vision and Ophthalmology, Annual Meeting
  • Place of Presentation: Fort Lauderdale, FL