| 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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| 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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