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2007 Fiscal Year Final Research Report Summary

Studies on autommune diseases in OSM deficient mice

Research Project

Project/Area Number 18390119
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

MIYAJIMA Atsushi  The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor (50135232)

Project Period (FY) 2006 – 2007
Keywordsknockout mouse / autoimmune disease / cytokine / dendritic cells / macrophage
Research Abstract

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease caused by immunological disorders and exhibits various clinical phenotypes. However, the mechanism of SLE development still remains unclear. We found that mice deficient for Oncostatin M (OSM), a member of IL-6 family, exhibit increased serum autoantibody levels and glomerulonephritis, we characterized OSM deficient mice to understand a cause of SLE. Histological analysis revealed that inflammation was observed in the lung and spleen and activated T cells infiltrated into the lung. Furthermore, arthritis of hind paw was observed in OSM-deficient male mice. These results indicated that OSM-deficient mice spontaneously develop SLE with inflammation in multiple organs. To address the relationship between OSM and autoimmunity, we examined the thymus of OSM-deficient mice and found thymic hypoplasia and altered thymic architecture. While T cells developed normally, numerous apoptotic thymocytes were detected in OSM-deficient thymus. Development of unique thymic macrophages with strong phagocytic activity was impaired in OSM-deficient mice, suggesting that autoantigens derived from thymus may be a cause of autoantibody production. Th1 response in peripheral immune response against LPS was augmented in OSM-deficient mice due to dysregulation of dendritic cells (DCs), indicating correlation of Th1 polarization and development of glomerulonephritis. To further analyze the abnormality of DC activation, we tried to identify factors involved in DC regulation by microarray analysis using OSM-deficient DCs. Currently, we are investigating functions of some candidate genes.

  • Research Products

    (34 results)

All 2009 2008 2007 2006 Other

All Journal Article (14 results) (of which Peer Reviewed: 6 results) Presentation (20 results)

  • [Journal Article] Oncostatin M regulates secretoglobin 3A1 and 3A2 expression in a bidirectional manner.2009

    • Author(s)
      Tomita T., Yamada A., Miyakoshi A., Kido T., Sheikh F., Srisodsai A., Miyajima A., Donnelly R. P., Kimura S.
    • Journal Title

      Am. J. Respir. Cell. Mol. Biol. 40

      Pages: 620-630

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Oncostatin M regulates secretoglobin 3A1 and 3A2 expression in a bidirectional manner.2009

    • Author(s)
      Tomita T., Yamada A., Miyakoshi A., Kido T., Sheikh F., Srisodsai A., Miyajima A., Donnelly R. P., Kimura S.
    • Journal Title

      Am. J. Respir. Cell. Mol Biol. 40

      Pages: 620-630

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oncostatin M Receptor-b Signaling Limits Monocytic Cell Recruitment in Acute Inflammation.2008

    • Author(s)
      Hams E, Colmont C. S., Dioszeghy V., Hammond V. J., Fielding C. A., Williams A. S., Tanaka M., Miyajima A., Taylor P. R., Topley N., Jones S. A.
    • Journal Title

      J. Immunol. 181(3)

      Pages: 2174-2180

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Oncostatin M Receptor-b Signaling Limits Monocytic Cell Recruitment in Acute Inflammation.2008

    • Author(s)
      Hams E, Colmont C. S., Dioszeghy V, Hammond V. J., Fielding C. A., Williams A. S., Tanaka M., Miyajima A., Taylor P. R., Topley N., Jones S. A.
    • Journal Title

      J. Immunol. 181(3)

      Pages: 2174-2180

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oncosatain M gene therapy attenuates liver damage induced by dimethynitorsoamine in rats.2007

    • Author(s)
      Hamada T., Sato A., Hirano T., Yamamoto T., Son G., Onodera M., Torii I., Nishigami T., Tanaka M., Miyajima A., Fujimoto J., Tsujimura T.
    • Journal Title

      Am. J. Pathol. 171(3)

      Pages: 872-81

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 胎児期胸腺におけるIL-18によるCD11b+樹状細胞の分化誘導2007

    • Author(s)
      伊藤寛明, 宮島篤
    • Journal Title

      臨床免疫・アレルギー科 46

      Pages: 250-255

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] オンコスタチン2007

    • Author(s)
      田中稔, 宮島篤
    • Journal Title

      Surgery Frontier 14 (2)

      Pages: 72-74

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differentiation of CDllb+ dendritic cells by IL-18 in fetal thvmus.2007

    • Author(s)
      Ito H., MiyajimaA.
    • Journal Title

      Clinical Immunology ・ Allergy 46

      Pages: 250-255

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oncostatin.2007

    • Author(s)
      Tanaka M., Miyaiima A.
    • Journal Title

      Surgery Frontier 14 (2)

      Pages: 72-74

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] IL-18 produced by thymic epithelial cells induces development of dendritic cells with CD11b in the fetal thymus2006

    • Author(s)
      Ito H., et al.
    • Journal Title

      Int. Immunol. 18(8)

      Pages: 1253-1263

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Oncostatin M Inhibits adipogenesis through Ras/ERK and STAT5 signaling pathways.2006

    • Author(s)
      Miyaoka Y., Tanaka M., Naiki T., Miyajima A.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 37913-37920

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] IL-18 produced by thymic epithelial cells induces development of dendritic cells with CDllb in the fetal thymus.2006

    • Author(s)
      Ito H., Esashi E., Akiyama T., Inoue J., Miyajima A.
    • Journal Title

      International Immunology 18(8)

      Pages: 1253-1263

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oncostatin M deficiency leads to thymic hypoplasia, accumulation of apoptotic thymocytes and glomerulonephrritis.

    • Author(s)
      Esashi E., Ito H., Minehata K., Saito S., Morikawa Y., Miyajima A.
    • Journal Title

      Eur. J. Immunol. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Oncostatin M deficiency leads to thymic hypoplasia, accumulation of apoptotic thymocytes and glomerulonephrritis.

    • Author(s)
      Esashi E., Ito H., Minehata K., Saito S., Morikawa Y, Miyajima A.
    • Journal Title

      Eur. J. Immunol in press

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Identification of a novel IkB family member and its role in innate immune responses.2009

    • Author(s)
      Yamauchi S., Ito H., Miyajima A.
    • Organizer
      The 96th Annual Meeting of The American Association of Immunologists (AAI)
    • Place of Presentation
      Seattle, Washington, U.S.A.
    • Year and Date
      20090508-20090512
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Identification of a novel IkB family member and its role in innate immune responses.2009

    • Author(s)
      Yamauchi S., Ito H., Miyajima A.
    • Organizer
      The 96th Annual Meeting of The American Association of Immunologists(AAI)
    • Place of Presentation
      Seattle, Washington
    • Year and Date
      20090508-20090512
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Identification and characterization of a novel immune response regulatory factor in macrophages.2008

    • Author(s)
      Yamauchi S., Ito H., Miyajima A. .
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20081201-20081203
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Identification and characterization of a novel immune response regulatory factor in macrophages.2008

    • Author(s)
      Yamauchi S., Ito H., Miyajima A.
    • Organizer
      The 38^<th> annual meeting of the Japanese Society for Immunology
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      20081201-20081203
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Role of Oncostatin M in dendritic cell function.2007

    • Author(s)
      Ito H., Esashi E., Miyajima A.
    • Organizer
      Keystone Symposia on Molecular and CellularBiology 2007 "Intracellular and Intercellular Signaling in Dendritic Cell Function " (J8)
    • Place of Presentation
      Keystone Restort, Colorado, U.S.A.
    • Year and Date
      20070225-20070301
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Role of Oncostatin M in dendritic cell function.2007

    • Author(s)
      Ito H., Esashi E., Miyajima A.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology 2007 "Intracellular and Intercellular Signaling in Dendritic Cell Function " (J8)
    • Place of Presentation
      Keystone Restart, Colorado, U.S.A.
    • Year and Date
      20070225-20070301
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Role of Oncostatin M in dendritic cell function.2006

    • Author(s)
      Ito H., Miyajima A.
    • Organizer
      第36回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪国際会議場(クラレキューブ大阪)
    • Year and Date
      20061211-20061213
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Anti-inflammatory activity of endothelial cells in LPS-induced end otoxin shock.2006

    • Author(s)
      Yamauchi S., Ito H., Miyajima A.
    • Organizer
      第36回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪国際会議場(グランキューブ大阪)
    • Year and Date
      20061211-20061213
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Role of Oncostatin M in dendritic cell function.2006

    • Author(s)
      Ito H., Miyajima A.
    • Organizer
      The 36^<th> annual meeting of the Japanese Society for Immunology
    • Place of Presentation
      Osaka International Convention Center (GRAND CUBE OSAKA) Osaka, Japan
    • Year and Date
      20061211-20061213
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Anti-inflammatory activity of endothelial cells in LPS-induced endotoxin shock.2006

    • Author(s)
      Yamauchi S., Ito H., Miyajima A
    • Organizer
      The 36^<th> annual meeting of the Japanese Society for Immunology
    • Place of Presentation
      Osaka International Convention Center (GRAND CUBE OSAKA) Osaka, Japan
    • Year and Date
      20061211-20061213
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Developmental stages of liver sinusoids and endothelial cells defmed by the expression of cell surface antigens.2006

    • Author(s)
      Nonaka H., Yamauchi S., Hirata A., Miyajima A.
    • Organizer
      20^<th> IUBMB (International Congress of Biochemistry and Molecular Biology) and 11^<th> FAOBMB Congress
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] IL-18 produced by thymic epithelial cells induces the development of dendritic cells with CD11b in the fetal thymus.2006

    • Author(s)
      Ito H., Esashi E, Akiyama T., Inoue J., Miyajima A.
    • Organizer
      20^<th> IUBMB (International Congress of Bloche mistry and Molecular Biology) and 11^<th> FAO BMB Congress
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Isolation and characterization of p75^<NTR> positive cells from mouse fetal liver.2006

    • Author(s)
      Suzuki K., Tanaka M., Watanabe N., Miyajima A.
    • Organizer
      20^<th> IUBMB (International Congress of Bioche mistry and Molecular Biology) and 11^<th> FAO BMB Congress
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] A role for Tim2 in hepatocyte differentiation.2006

    • Author(s)
      Watanabe N., Tanaka M., Suzuki K., Kumanogoh A., Kikutani H., Miyaiima A.
    • Organizer
      20^<th> IUBMB (International Congress of Bioche mistry and Molecular Biology) and 11^<th> FAO BMB Congress
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Inhibition of adipocyte differentiation by Oncostatin M (OSM).2006

    • Author(s)
      Miyaoka Y., Tanaka M., Miyajima A.
    • Organizer
      20^<th> IUBMB (International Congress of Bioche mistry and Molecular Biology) and 11^<th> FAO BMB Congress
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Developmental stages of liver sinusoids and endothelial cells defined by the expression of cell surface antigens.2006

    • Author(s)
      Nonaka H., Yamauchi S., Hirata A., Miyajima A.
    • Organizer
      20^<th> IUBMB(International Congress of Biochemistry and Molecular Biology) and 11^<th> FAOBMB Congress
    • Place of Presentation
      Kyoto JAPAN
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] IL-18 produced by thymic epithelial cells induces the development of dendritic cells with CDllb in the fetal thymus.2006

    • Author(s)
      Ito H., Esashi E, Akiyama T., Inoue J., Miyajima A.
    • Organizer
      20^<th> IUBMB(International Congress of Biochemistry and Molecular Biology) and 11^<th> FAOBMB Congress
    • Place of Presentation
      Kyoto JAPAN
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Isolation and characterization of p75^<NTR> positive cells from mouse fetal liver.2006

    • Author(s)
      Suzuki K., Tanaka M., Watanabe N., Miyajima A.
    • Organizer
      20^<th> IUBMB(International Congress of Biochemistry and Molecular Biology) and 11^<th> FAOBMB Congress
    • Place of Presentation
      Kyoto JAPAN
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] A role for Tim2 in hepatocyte differentiation.2006

    • Author(s)
      Watanabe N., Tanaka ML, Suzuki K., Kumanogoh A., Kikutani H., Miyajima A.
    • Organizer
      20^<th> IUBMB(International Congress of Biochemistry and Molecular Biology) and 11^<th> FAOBMB Congress
    • Place of Presentation
      Kyoto JAPAN
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Inhibition of adipocyte differentiation by Oncostatin M (OSM).2006

    • Author(s)
      Miyaoka Y., Tanaka M., Miyajima A.
    • Organizer
      20^<th> IUBMB(International Congress of Biochemistry and Molecular Biology) and 11^<th> FAOBMB Congress
    • Place of Presentation
      Kyoto JAPAN
    • Year and Date
      20060618-20060623
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-06-09  

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