Studies on autommune diseases in OSM deficient mice

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18390119
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAJIMA Atsushi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor (50135232)
• Project Period (FY): 2006 – 2007
• Keywords: knockout 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

• [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 thymus (2006)
  • 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