| Project/Area Number |
16590400
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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 Tokyo |
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Principal Investigator |
AKIYAMA Taishin The University of Tokyo, Institute of Medical Science, Lecturer, 医科学研究所, 講師 (50327665)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Jun-ichiro The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (70176428)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Autoimmune disease / Thymus / NF-κB / TNF receptor / Regulatory T cells / autoantibody / TRAF / Stroma cells / 自己免疫 / T細胞 / リンパ器官 |
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| Research Abstract |
The goal of this research project is to elucidate the molecular mechanism in the differentiation of medullary thymic epithelial cells (mTEC) and in the tolerance induction by mTEC. For this purpose, we especially focused on the analyzes of TRAF6-deficient mice, which have inflammatory cell infiltrate in the several organs in addition to thymic atrophy.
In 2004, we manifested that TRAF6 is essential for the development of mTEC and that TRAF6 in thymic stroma is required for the induction of self-tolerance by thymus. Thus, we performed the transplantation of thymic stroma obtained from TRAF6-deficient embryo and control embryo on the kidney capsule of athymic nude mice. The medullar architecture was disorganized in the grafted thymi from TRAF6-deficient mice. Nude mice grafted with TRAF6-deficient thymic stroma showed inflammatory cell infiltrates in the organs such as lung, liver, kidney, and pancreas. In addition, the nude mice carrying TRAF6-deficient grafted thymus had autoantibodies against these organs in the serum. From these results, we concluded that TRAF6 regulates the differentiation of mTEC and the induction of thymic stroma-dependent self-tolerance.
In 2005, we determined the possible candidates of the cell surface receptors on mTEC that utilize TRAF6 as a signal transduction molecule by the screening of the members of TNF receptor superfamily on the expression of embryonic thymic stroma. In addition, we found that TRAF6 is involved in the differentiation of CD4^+CD25^+ regulatory T cells in thymus
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