Studies on autommune diseases in OSM deficient mice
| Project/Area Number |
18390119
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIYAJIMA Atsushi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor (50135232)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,230,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | knockout mouse / autoimmune disease / cytokine / dendritic cells / macrophage |
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| 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.
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Report
(3 results)
Research Products
(38 results)
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[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.
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Journal Title
J. Immunol. 181(3)
Pages: 2174-2180
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[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.
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Journal Title
J. Immunol. 181(3)
Pages: 2174-2180
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Oncostatin M Receptor-b Signaling Limits Monocytic Cell Recruitment in Acute Inflammation2008
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.
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Journal Title
J. Immunol 181(3)
Pages: 2174-2180
Related Report
Peer Reviewed
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[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.
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Journal Title
Am. J. Pathol. 171(3)
Pages: 872-81
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[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.
Description
「研究成果報告書概要(和文)」より
Related Report
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[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.
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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
Description
「研究成果報告書概要(和文)」より
Related Report
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[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
Description
「研究成果報告書概要(欧文)」より
Related Report
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