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関節リウマチの遺伝要因の解明

Research Project

Project/Area Number 13204012
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (C)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

岩倉 洋一郎  東京大学, 医科学研究所, 教授 (10089120)

Co-Investigator(Kenkyū-buntansha) 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)
森本 幾夫  東京大学, 医科学研究所, 教授 (30119028)
Project Period (FY) 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2001: ¥6,500,000 (Direct Cost: ¥6,500,000)
KeywordsHTLV-I / IL-1 / IL-6 / IL-1レセプターアンタゴニスト / 関節リウマチ / ノックアウトマウス / トランスジェニックマウス
Research Abstract

我々は、HTLV-I遺伝子を導入したTgマウスを作製し、このウイルスが関節リウマチによく似た自己免疫性の関節炎を引き起こすことを見いだした。また、この関節炎の発症にはIL-1やIL-6などのサイトカインの過剰発現が重要な役割を果たしていることを示し、さらにIL-1レセプターアンタゴニスト(IL-1Ra)KOマウスも同様の自己免疫性の慢性関節炎になることを示した。これら何れのモデルにおいても発症はBALB/c背景で非常に高く、C57BL/6背景ではほとんど発症しない。本研究ではこれらの結果をふまえ、1)IL-1Raの機能不全がヒトの関節リウマチでも病因となっているか2)関節炎の発症に対する系統間の感受性に関与している遺伝子は何か、を明らかにすることを目的とした。その結果、1)については、患者の了解の元にの500検体の血清中のIL-1Ra蛋白質の量を定量した結果、15検体が異常に低い値を示した。そこで、今後は遺伝子の発現量や構造などに変化がないか解析を行っていきたい。また、2)については、いくつかの染色体に連鎖が見いだされたので、今後その領域を詳細にマップしていく予定である。

Report

(1 results)
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] 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)

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

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      2001 Annual Research Report
  • [Publications] Seino, K: "Requirement for NKT cells in the induction of allograft tolerance"Proc. Natl. Acad. U. S.. 98. 2577-2581 (2001)

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      2001 Annual Research Report
  • [Publications] Ishii 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)

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      2001 Annual Research Report
  • [Publications] Naruse-Nakajima, C: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1"Mecha. Develop. 102. 95-105 (2001)

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      2001 Annual Research Report
  • [Publications] Ozaki, H: "Six-4,a putative myogenin gene regulator, is not essential for mouse embiyonal development"Mol. Cell. Biol. 24. 3343-3350 (2001)

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      2001 Annual Research Report
  • [Publications] 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 piasma glycoproteins"Biochem J.. 357. 827-834 (2001)

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      2001 Annual Research Report
  • [Publications] Boutin, H.: "Role of IL-1α and IL-β in ischaemic brain damage"J. Neuroscience. 21. 5528-5534 (2001)

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      2001 Annual Research Report
  • [Publications] 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)

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      2001 Annual Research Report
  • [Publications] Sato, M: "Th1 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)

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      2001 Annual Research Report
  • [Publications] Imaizumi, Y: "Increased expression of interleukin-1β in mouse hippocampus after global cerebral ischemia"Acta Histochem. Cytochem.. 34. 357-362 (2001)

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      2001 Annual Research Report
  • [Publications] Dal, J. H.: "Glycyrrhizin enhances interleukin-12 production in peritoneal macrophage"Immunology. 103. 235-243 (2001)

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      2001 Annual Research Report
  • [Publications] Norose, K: "Organ infectivity of Toxoplasma gondii in interferon-γ knockout mice"J. Parasitol. 87. 447-452 (2001)

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      2001 Annual Research Report
  • [Publications] Yoneto, T: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection"J. Immunol.. 166. 6236-6241 (2001)

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      2001 Annual Research Report
  • [Publications] Hayakawa, Y: "Critical contribution of IEN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide"Eur J Immunol. 31. 1720-1727 (2001)

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

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  • [Publications] Nakae, S: "IL-1 enhances T cell-dependent antibody production through induction of CD4OL and 0X40 on T cells"J. Immunol.. 167. 90-97 (2001)

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      2001 Annual Research Report
  • [Publications] Yasuda, J: "T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr"Virology. 285. 181-192 (2001)

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

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  • [Publications] 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)

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      2001 Annual Research Report
  • [Publications] Nakae, S: "IL-1α, 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)

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      2001 Annual Research Report
  • [Publications] Kyuwa, S.: "The seventy 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)

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

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      2001 Annual Research Report
  • [Publications] Yokoyama, H.: "Pathological changes of renal epithelial cells in mice transgenic for the U virus ORF1 gene"J. Gen. Virol.. 83. 141-150 (2002)

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      2001 Annual Research Report
  • [Publications] Saijo, S.: "Suppression of autoimmune arthritis in IL-I-deficient mice in which T cell activation is impaired due to low levels of CD40L and 0X40 expression on T cells"Arth. Rheum.. 46. 533-544 (2002)

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      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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