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(In Japanese)遺伝子改変に基づく生体防御システムの解明

Research report code R000000135
Posted date Sep 30, 2002
  • (In Japanese)審良 静男
  • (In Japanese)大阪大学微生物病研究所
Research organization
  • (In Japanese)大阪大学微生物病研究所
Report name (In Japanese)遺伝子改変に基づく生体防御システムの解明
Technology summary (In Japanese)遺伝子欠損マウスを作製することにより,炎症や免疫反応にかかわる分子の生体における役割を研究している。Toll-like receptor(TLR)ファミリー欠損マウスとその解析を行ない,TLR2,TLR4がそれぞれ微生物細胞膜成分の異なる分子を認識する受容体であることを明らかにした。TLR2はLPS以外の細菌菌体成分を認識する受容体であること,マイコプラズマ菌のリポペプチドを認識する受容体であることが分かった。また,マクロファージにおけるLPSトレランスは,主にTLR4受容体のダウンレギュレーションに起因することが分かった。さらに,データベースを用いて新規のTLRファミリーを同定し,TLR7,TLR8,TLR9,TLR10,TLR11と命名し,各メンバーのノックアウトマウスを作製するためにゲノムのクローニングを行なった。
Research field
  • Immunological reaction in general
  • Receptors on cell membrane
  • Microorganism biochemistry
  • Animal biochemistry
Published papers related (In Japanese)(1)Kawai, T., Adachi, O., Ogawa, T., Takeda, K. and Akira, S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity, 11, 115-122,1999.
(2)Hayashi, N., Matsui, K., Tsutui, H., Osada, Y., Mohamed, R., Kashiwamura, S.-I., Hyodo, Y., Takeda, K., Akira, S., Hada, T., Higashino, K., Kojima, S. and Nakanishi, K. Kupffer cells from Schistosoma mansoni-infected mice are responsible for prompt type-2-differentiation of hepatic T cells in response to worm antigens. J. Immunol., 163, 6702-6711, 1999.
(3)Tsutsui, H., Kayagaki, N., Kuida, K., Nakano, Y., Hayashi, N., Takeda, K., Matsui, K., Kashiwamura, S.-I., Hada, T., Akira, S., Yagita, H., Okamura, H. and Nakanishi, K. Caspase-1-independent Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity, 11, 359-367, 1999.
(4)Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., Takeda, K. and Akira, S. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity, 11,443-451, 1999.
(5)Kaisho, T., Tsutsui, H., Tanaka, T., Tujimura, T., Takeda, K., Kawai, T., Yoshida, N., Nakanishi, K. and Akira, S. Impairment of natural killer cytotoxic activity and interferon-γ production in C/EBP γ-deficient mice. J. Exp. Med., 190, 1673-1582, 1999.
(6)Hoshino, K., Kashiwamura, S.-I., Kuribayashi, Y., Kodama, T., Tujimura, T., Nakanishi, K., Matsuyama, T., Tadeka, K. and Akira, S. Absence of IL-1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function. J. Exp. Med., 190, 1541-1548, 1999.
(7)Yoshimoto, T., Tsutsui, H., Tominaga, K., Hoshino, K., Okamura, H., Akira, S., Paul, W.E. and Nakanishi, K. IL-18, although anti-allergic when administered with IL-12, stimulates IL-4 and histamine release by basophils. Proc. Natl. Acad. Sci. USA, 96, 13962-13966, 1999.
(8)Matsumoto, M., Tanaka, T., Kaisho, T., Sanjo, H., Copeland, N.G., Gilbert, D. J., Jenkins, N.A. and Akira, S.A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages. J.Immunol., 163, 5039-5048, 1999.
(9)Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S. and Takeda, J. Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J., 18, 4657-4668, 1999.
(10)Takeuchi, O., Takeda, K., Hoshino, K., Adachi, O., Ogawa, T. and Akira, S. Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol., 12, 113-117, 2000.
(11)Takeuchi, O., Kaufmann, A., Grote, K., Kawai, T., Hoshino, K., Morr, M. Muhlradt, P.F. and Akira, S. Preferentially the R-steroisomer of the mycoplasmal lipopeptide MALP-2 activates immune cells through a Toll-like receptor 2- and MyD88-dependent signalling pathway. J. Immunol., 164,554-557, 2000.
(12)Takeuchi, S., Takeda, K., Oishi, K., Nomi, M., Ikeya, M., Itoh, K., Tamura, S., Ueda, T., Hatta, T., Otani, H., Terashima, T., Takeda, S., Yamamura, H., Akira, S. and Minami, Y. Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation. Genes Cells, 5, 71-78, 2000.
(13)Nomura, F., Akaishi, Y., Sakao, Y., Sato, S., Kawai, T., Matsumoto, M., Nakanishi, K., Kimoto, M., Miyake, K., Takeda, K. and Akira, S. Endotoxin tolerance in mouse peritoneal macrophages correlates with downregulation of surface Toll-like receptor 4 expression. J. Immunol., 164, 3476-3479, 2000.
(14)Nomura, F., Kawai, T., Nakanishi, K. and Akira, S. NF- κB activation through IKK-i-dependent I-TRAF/TANK phosphorylation. Genes Cells, 5, 191-202, 2000.
(15)Okusu, K., Yoshimoto, T., Takeda, K., Ogura, T., Kashiwamura, S.-I., Iwakura, Y., Akira, S., Okamura, H. and Nakanishi, K. Potentiality of interleukin-18 as auseful reagent for treatment and prevention of Leishmania major infection. Infect. Immun., 68, 2449-2456, 2000.
Research project
  • Core Research for Evolutional Science and Technology;Host Defense Mechanism
Information research report
  • (In Japanese)審良 静男. 生体防御のメカニズム 遺伝子改変に基づく生体防御システムの解明. 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.143 - 146.