| Project/Area Number |
17590435
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MATSUSHIMA Akemi The University of Tokushima, Faculty of Medicine, assistant professor (70116862)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Mitsuru The Univesity of Tokushima, Institute for Enzyme Research, Professor (60221595)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | autoimmune diseases / AIRE / Aire-deficient mice / thymic epithelial cell / 自己抗原 / MHC |
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| Research Abstract |
Autoimmune diseases are influenced by environmental factors and/or genetic predisposition so the situation seems to have become more complicated. In this regard, only a small number of genes genetically relevant to the pathogenetic processes for the development of autoimmune diseases have been found, genetic engineering of such genes in mice should enable us to establish disease models and facilitate an understanding of the disease mechanisms to a large extent. AIRE is expressed in thymic epithelial cells (mTEC) and monocyte-dendritic cell lineage of the thymus. Both cell types are considered to play major roles in establishment of self-tolerance by eliminating autoreactive T cells. We have generated Aire-deficient mice by gene targeting and backcrossed to NOD mice or BALB/c mice or C57BL/6 mice for over 10 generations. In Aire-deficient NOD mice, the degree of lymphoid cell infiltration of the organs affected in the original NOD mice was much more severe in Aire-deficient NOD mice. And we also observed lymphoid cell infiltration in many other organs of Aire-deficient NOD mice, including liver, lung, and thyroid gland, in which we usually do not observe changes in the orginal NOD mice. Thus, abrogation of Aire in NOD mice resulted in expansion of spectrum of target organs destroyed by autoimmune attack together with an alteration of intra-pancreatic target-organ. To confirm the factors that determine the target organs, we did Aire-deficient embryos thymic grafting to BALB/c nude mice which induced the same pathology as Aire-deficient NOD mice. But the bone marrow transfer of Aire-deficient NOD mice to NOD mice had no effects. On the other hand, the auto-antibody in the serum were induced by bone marrow transfer. These results indicate that autoimmune diseases of Aire-deficient mice are mediated by thymus medulla and bone marrow.
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