2001 年度実績報告書

IL-1による免疫応答制御機構の解明

研究課題

研究課題/領域番号	13037010
研究種目	特定領域研究(A)
研究機関	東京大学
研究代表者	岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)
研究分担者	須藤カツ子東京大学, 医科学研究所, 助手 (50126091) 宝来玲子東京大学, 医科学研究所, 助手 (20313091)
キーワード	免疫応答 / 発生工学 / 自己免疫 / T細胞
研究概要	代表者らは、発生工学的手法を用いて、IL-1が抗体産生に重要な役割を果たすこと、IL-1レセプターアンタゴニスト(IL-1Ra)の欠損によりIL-1システムの制御が破綻すると自己免疫疾患が誘導されることを明らかにした。本研究では、免疫応答におけるIL一1シグナルの役割、及びその調節機構を明らかにし、IL-1システムの制御異常が自己免疫性疾患を誘導する機構を解明することを目的とした。 1)免疫応答調節におけるIL-1Raの役割 IL-1Ra欠損による自己免疫起因性の免疫担当細胞、炎症性サイトカインを同定し、これらのシグナルを中和することによる自己免疫抑制効果を検討した。 1.免疫担当細胞の役割:骨髄細胞の移入実験、T細胞の移入実験により、T細胞が関節炎発症に重要であることを明らかにした。また、IL-1によるT細胞の活性化には、CD40-CD40L、OX40-OX40L経路が関与することが示唆されたので、IL-1RaKOマウスにこれらの副シグナル経路を中和する抗体投与を行い、関節炎の発症が抑制されることを明らかにした。 2.炎症性サイトカインの役割:IL-1RaKOマウスの関節で発現が亢進しているTNFα、IL-6について、それぞれを欠損するIL-1RaKOマウスを作製し、TNFα欠損が関節炎を強く抑制することを明らかにした。 2)T細胞依存性免疫反応におけるIL-1の役割 T細胞依存性抗体産生応答にIL-1が重要な役割を果たすこと、抗原特異的なT細胞の活性化にIL-1の下流でCD40-CD40L及びOX40-OX40L経路が働くことを明らかにした。次に、T細胞が媒介する免疫反応として接触型過敏症(CHS)反応におけるIL-1の役割を検討し、CHSの感作期と誘発期いずれにも関与していることを明らかにした。

研究成果
(25件)

すべてその他

すべて文献書誌 (25件)

[文献書誌] Takeda, K: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells"Nature Medicine. 7. 94-100 (2001)
[文献書誌] Fukamauchi, F: "TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus"Biochem.Biphys.Res Commun. 281. 220-226 (2001)
[文献書誌] Seino, K: "Requirement for NKT cells in the induction of allograft tolerance"Proc.Nati.Acad.U.S.. 98. 2577-2581 (2001)
[文献書誌] Ishui, T: "Projection of three subsets of olfactory neurons expressing the odorant receptor transgene and the two cognate endogenous alleles"Genes to Cell. 6. 71-78 (2001)
[文献書誌] Naruse-Nakajima, C: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1"Mecha.Develop. 102. 95-105 (2001)
[文献書誌] Ozaki, H: "Six-4, a putative myogenin gene regulator, is not essential for mouse embryonal development"Mol.Cell.Biol. 21. 3343-3350 (2001)
[文献書誌] Boutin, H.: "Role of IL-1α and IL-1β in ischaemic brain damage"J.Neuroscience. 21. 5528-5534 (2001)
[文献書誌] Morita, Y: "Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated(Atm)gene function"Cell Death Differ.. 8. 614-620 (2001)
[文献書誌] Sato, M: "Thl cytokine-conditioned bone marrow-derived dendritic cells can bypass the requirement for Th functions during the generation of CD8(+) CTL"J.Immunol.. 167. 3687-3691 (2001)
[文献書誌] Imaizumi, Y: "Increased expression of interleukin-1β in mouse hippocampus after global cerebral ischemia"Acta Histochem.Cytochem.. 34. 357-362 (2001)
[文献書誌] Dal, J. H.: "Glycyrrhizin enhances interleukin-12 production in peritoneal macrophage"Immunology. 103. 235-243 (2001)
[文献書誌] Miura, T.: "Effect of 6-Hydroxydopamine on host resistance against Listeria monocytogenes infection"Infect.Immun.. 69. 7234-7241 (2001)
[文献書誌] Le Feuvre, R. A: "Priming of macrophages with LPS potentiates P2X7 mediated cell death via a caspase-1 dependent mechanism, independently of cytokine production"J.Biol.Chem. (2001)
[文献書誌] Norose, K: "Organ infectivity of Toxoplasma gondii in interferon-γ knockout mice"J.Parasitol. 87. 447-452 (2001)
[文献書誌] Yoneto, T: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the hos resistance to blood-stage Plasmodium berghei XAT infection"J, Immunol.. 166. 6236-6241 (2001)
[文献書誌] Hayakawa, Y: "Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide"Eur J Immunol. 31. 1720-1727 (2001)
[文献書誌] Shibata, S: "Cloning of a novel 2',5'-oligoadenylate synthetase-like molecule, Oasl5 in mice"Gene. 271. 261-271 (2001)
[文献書誌] Nakae, S: "IL-1 enhances T cell-dependent antibody production through induction of CD4OL and OX40 on T cells"J.Immunol.. 167. 90-97 (2001)
[文献書誌] Yasuda, J: "T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr"Virology. 285. 181-192 (2001)
[文献書誌] Kotani, N: "Knockout of mouse β1,4-galactosyltransferase-1 gene results in a dramatic shift of outer chain moieties of N-glycans from type 2 to type 1 chains in hepatic membrane and plasma glycoproteins"Biochem J.. 357. 827-834 (2001)
[文献書誌] Nakae, S: "IL-lα, but not IL-1β, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity"Int. Immunol.. 13. 1471-1478 (2001)
[文献書誌] Kyuwa, S.: "The severity of hepatic lesion after intraperitoneal JHMV infection in IFN-gamma deficient mice is parallel to viral replication in hepatocytes in vitro"Adv Exp Med Biol.. 494. 95-99 (2001)
[文献書誌] Moshkin, M. P.: "Social behavior in male mice deficient in genes for interleukin-1"Med.Immunolo.. 3. 449-457 (2001)
[文献書誌] Yokoyama, H.: "Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene"J.Gen.Virol.. 83. 141-150 (2002)
[文献書誌] Saijo, S.: "Suppression of autoimmune arthritis in IL-1-deficient mice in which T cell activation is impaired due to low levels of CD4OL and 0X40 expression on T cell"Arth.Rheum.. 46. 533-544 (2002)

2001 年度 実績報告書

IL-1による免疫応答制御機構の解明

研究代表者

岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)

研究成果

[文献書誌] Takeda, K: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells"Nature Medicine. 7. 94-100 (2001)

[文献書誌] Fukamauchi, F: "TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus"Biochem.Biphys.Res Commun. 281. 220-226 (2001)

[文献書誌] Seino, K: "Requirement for NKT cells in the induction of allograft tolerance"Proc.Nati.Acad.U.S.. 98. 2577-2581 (2001)

[文献書誌] Ishui, T: "Projection of three subsets of olfactory neurons expressing the odorant receptor transgene and the two cognate endogenous alleles"Genes to Cell. 6. 71-78 (2001)

[文献書誌] Naruse-Nakajima, C: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1"Mecha.Develop. 102. 95-105 (2001)

[文献書誌] Ozaki, H: "Six-4, a putative myogenin gene regulator, is not essential for mouse embryonal development"Mol.Cell.Biol. 21. 3343-3350 (2001)

[文献書誌] Boutin, H.: "Role of IL-1α and IL-1β in ischaemic brain damage"J.Neuroscience. 21. 5528-5534 (2001)

[文献書誌] Morita, Y: "Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated(Atm)gene function"Cell Death Differ.. 8. 614-620 (2001)

[文献書誌] Sato, M: "Thl cytokine-conditioned bone marrow-derived dendritic cells can bypass the requirement for Th functions during the generation of CD8(+) CTL"J.Immunol.. 167. 3687-3691 (2001)

[文献書誌] Imaizumi, Y: "Increased expression of interleukin-1β in mouse hippocampus after global cerebral ischemia"Acta Histochem.Cytochem.. 34. 357-362 (2001)

[文献書誌] Dal, J. H.: "Glycyrrhizin enhances interleukin-12 production in peritoneal macrophage"Immunology. 103. 235-243 (2001)

[文献書誌] Miura, T.: "Effect of 6-Hydroxydopamine on host resistance against Listeria monocytogenes infection"Infect.Immun.. 69. 7234-7241 (2001)

[文献書誌] Le Feuvre, R. A: "Priming of macrophages with LPS potentiates P2X7 mediated cell death via a caspase-1 dependent mechanism, independently of cytokine production"J.Biol.Chem. (2001)

[文献書誌] Norose, K: "Organ infectivity of Toxoplasma gondii in interferon-γ knockout mice"J.Parasitol. 87. 447-452 (2001)

[文献書誌] Yoneto, T: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the hos resistance to blood-stage Plasmodium berghei XAT infection"J, Immunol.. 166. 6236-6241 (2001)

[文献書誌] Hayakawa, Y: "Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide"Eur J Immunol. 31. 1720-1727 (2001)

[文献書誌] Shibata, S: "Cloning of a novel 2',5'-oligoadenylate synthetase-like molecule, Oasl5 in mice"Gene. 271. 261-271 (2001)

[文献書誌] Nakae, S: "IL-1 enhances T cell-dependent antibody production through induction of CD4OL and OX40 on T cells"J.Immunol.. 167. 90-97 (2001)

[文献書誌] Yasuda, J: "T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr"Virology. 285. 181-192 (2001)

[文献書誌] Kotani, N: "Knockout of mouse β1,4-galactosyltransferase-1 gene results in a dramatic shift of outer chain moieties of N-glycans from type 2 to type 1 chains in hepatic membrane and plasma glycoproteins"Biochem J.. 357. 827-834 (2001)

[文献書誌] Nakae, S: "IL-lα, but not IL-1β, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity"Int. Immunol.. 13. 1471-1478 (2001)

[文献書誌] Kyuwa, S.: "The severity of hepatic lesion after intraperitoneal JHMV infection in IFN-gamma deficient mice is parallel to viral replication in hepatocytes in vitro"Adv Exp Med Biol.. 494. 95-99 (2001)

[文献書誌] Moshkin, M. P.: "Social behavior in male mice deficient in genes for interleukin-1"Med.Immunolo.. 3. 449-457 (2001)

[文献書誌] Yokoyama, H.: "Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene"J.Gen.Virol.. 83. 141-150 (2002)

[文献書誌] Saijo, S.: "Suppression of autoimmune arthritis in IL-1-deficient mice in which T cell activation is impaired due to low levels of CD4OL and 0X40 expression on T cell"Arth.Rheum.. 46. 533-544 (2002)

2001 年度実績報告書

岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)