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(In Japanese)免疫系と神経・内分泌系の立体的分子機構の解明

Research report code R000000138
Posted date Sep 30, 2002
  • (In Japanese)奥村 康
  • (In Japanese)順天堂大学医学部
Research organization
  • (In Japanese)順天堂大学医学部
Report name (In Japanese)免疫系と神経・内分泌系の立体的分子機構の解明
Technology summary (In Japanese)ヒトTRAILが抗CD3抗体+IFNα/β処理により末梢リンパ球にTRAILの発現誘導が認められ,ヒト腎癌細胞におけるIFNα/β治療により誘導される腫瘍破壊の一つのメカニズムであることが明らかとなった。TNFレセプターを介するシグナル伝達系にはTRAF2とTRAF5が関与しており,一部のシグナル伝達はTRAF2とTRAF5が相補的に働いていることが初めて明らかとなった。NK細胞の一つの活性化のメカニズムを明らかにし,NKT細胞がConA誘導性肝炎の発病に必須の細胞であることを明らかにした。OX40/OX40L相互作用がリーシュマニア寄生虫感染症におけるTh2反応に必須の分子であることを明らかにした。免疫系の恒常性維持におけるIL-1raの役割を明らかにするためにIL-1raKOマウスを作製した。IL-1raノックアウトマウスはBalb/cバックグラウンドにすることにより,ほぼ100%関節炎を発病した。
Research field
  • Immunological reaction in general
  • Tumor immunity
  • Antigens, antibodies, complements in general
  • Cell physiology in general
  • Chemistry, biochemistry and pathology of tumors (=neoplasms)
Published papers related (In Japanese)(1)Morimoto, S., Y. Kanno, Y. Tanaka, Y. Tokano, H. Hashimoto, S. Jacquot, C. Morimoto, S.F. Schlossman, H. Yagita, K. Okumura, and T. Kobata. CD134L engagement enhances human B cell Ig production: CD154/CD40, CD70/CD27, and CD134/CD134L interactions coordinately regulate T cell-dependent B cell responses. J Immunol. 164:4097-104, 2000.
(2)Satake, Y., H. Akiba, K. Takeda, M. Atsuta, H. Yagita, and K. Okumura. Characterization of rat OX40 ligand by monoclonal antibody. Biochem Biophys Res Commun. 270:1041-8, 2000.
(3)Takeda, K., H. Oshima, Y. Hayakawa, H. Akiba, M. Atsuta, T. Kobata, K. Kobayashi, M. Ito, H. Yagita, and K. Okumura. CD27-mediated activation of murine NK cells. J Immunol. 164:1741-5, 2000.
(4)Tsukada, N., H. Akiba, T. Kobata, Y. Aizawa, H. Yagita, and K. Okumura. Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation. Blood. 95:2434-9, 2000.
(5)Akiba, H., Miyahira, Y., Atsuta, M., Takeda, K., Nohara, C., Futagawa, T., Matsuda, H., Aoki, T., Yagita, H. and Okumura, K. Critical contribution of OX40 ligand to T helper 2 cell type 2 differentiation in experimental leishmaniasis. J. Exp. Med. 191:375-380, 2000.
(6)Nakano H., S. Sakon, H. Koseki, T. Takemori, K. Tada, M. Matsumoto, E. Munechika, T. Sakai, T. Shirasawa, H. Akiba, T. Kobata, S.M. Santee, C.F. Ware, P.D. Rennert, M. Taniguchi, H. Yagita, and K. Okumura. Targeted Disruption of Traf5 gene Causes Defects in CD40- and CD27-mediated Lymphocyte Activation. Proc. Natl. Acad. Sci. USA 96; 9803-9808, 1999.
(7)Tsukada, N., T. Kobata, Y. Aizawa, H. Yagita, and K. Okumura. Graft-versus-leukemia (GVL) effect and graft-versus-host disease(GVHD) can be differentiated by cytotoxic mechanisms in a murine model of allogeneic bone marrow transplantation. Blood, 93: 2738-2747, 1999.
(8)Suzuki, N., A. Nakajima, S. Yoshino, K. Matsushima, H. Yagita, and K. Okumura Selective accumulation of CCR5+ T lymphocytes into inflamed jount of rheumatoid arthritis. Int. Immunol., 11:553-559, 1999.
(9)Kayagaki, N., N. Yamaguchi, M. Nakayama, A. Kawasai, H. Akiba, K. Okumura, and H. Yagita Involvement of TRAIL in human CD4+ T cell-mediated cytotoxicity. J. Immunol., 162; 2639-2647, 1999.
(10)Kayagaki, N., Yamaguchi, N., Nakayama, M., Eto, H., Okumura, K. and H. Yagita. Type I Interferones (IFNs) Regulate Tumor Necrosis Factor-related Apoptosis-inducing Ligand(TRAIL) Expression on Human T Cells: A Novel Mechanism for the Antitumor Effects of Type I IFNs. J. Exp. Med. 189:1451-1460, 1999.
(11)Kodama, T., K. Takeda, O. Shimozato, Y. Hayakawa, M. Atsuta, K. Kobayashi, M. Ito, H. Yagita, and K. Okumura. Perforin-dependent NK cell cytotoxicity is sufficient for anti-metastatic effect of IL-12. Eur. J. Immunol. 29:1-7, 1999.
(12)Hatakeyama, S., M. Kitagawa, K. Nakayama, M. Shirane, M. Matsumoto, K. Hattori, H. Higashi, H. Nakano, K. Okumura, K. Onoe, R.A. Good, and K.-I. Nakayama. Ubiquitin-dependent degradation of IκB is mediated by a novel ubiquitin ligase SCFFWD1. Proc. Natl. Acad. Sci. 96: 3859-3863, 1999.
(13)Shimozato, O., K. Takeda, H. Yagita, and K. Okumura Expression of CD30 ligand (CD153) on murine activated T cells. Biochem. Biophys. Res. Commun. 256: 519-526, 1999.
(14)Akiba, H., H. Oshima, K. Takeda, M. Atsuta, H. Nakano, A. Nakanjima, C. Nohara, H. Yagita, and K. Okumura. CD28-independent costimulation of T cells by OX40 ligand and CD70 on activated B cells. J. Immunol. 162: 7058-7066, 1999.
(15)Kayagaki, N., Yamaguchi, N., Nakayama, M., Takeda, K., Akiba, H., Tsutsui, H., Okamura, H., Nakanishi, K., Okumura, K. and H. Yagita. Expression and Function of TNF-related Apoptosis-Inducing Ligand on Murine Activated NK Cells. J. Immunol. 163:1906-1913, 1999.
(16)Tsurui, H., Lerner, J.M., Takahashi, K., Hirose, S., Mitsui, K., Okumura, K. and Shirai, T.: Hyperspectral imaging of pathology samples. Proceedings of Three-Dimentional and Multidimensional Microscopy: Image Acquisition and Processing VI. Volume 3605, 273-281, 1999.
(17)Tsurui, H., Nishimura, H., Hattori, S., Hirose, S., Okumura K. and Shirai, T. Sevencolor Fluorescence Imaging of Tissue Samples Based on Fourier Spectroscopy and Singular Value Decomposition. J. Histo. Cyto., 48: 653-662, 2000.
(18)Takumi, T., Y. Nagamine, S. Miyake, C. Matsubara, K. Taguchi, S. Takekida, Y. Sakakida, K. Nishikawa, T. Kishimoto, S. Niwa, K. Okumura and H. Okamura. A mammalian ortholog of Drosophila timeless, highly expressed in SCN and retina, forms a complex with mPER1. Genes Cells, 4,67-75,1999.
Research project
  • Core Research for Evolutional Science and Technology;Host Defense Mechanism
Information research report
  • (In Japanese)奥村 康. 生体防御のメカニズム 免疫系と神経・内分泌系の立体的分子機構の解明. 戦略的基礎研究推進事業 平成11年度 研究年報.科学技術振興事業団, 2000. p.157 - 162.