Eludicating mechanisms how tissue-specific and type-specific inflammation are occurred in autoimmune diseases
| Project/Area Number |
17H06626
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Murakami Ryuichi 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (60800505)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 制御性T細胞 / 組織特異性 / 自己免疫疾患 / TCRレパトア / 樹状細胞サブセット / 樹状細胞 / T細胞受容体 |
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| Outline of Final Research Achievements |
Some autoimmune diseases occur in a tissue-specific manner. However, it remains elusive how the specificity is controlled. In our body, there is two T cell subsets. One is conventional T cells (Tconv) which promote immune responses, the other is regulatory T cells (Treg) which suppress immune responses. These T cells forms massive diversity of T cell receptor (TCR) repertoire, which enables immune systems to recognize various antigens. In the present study, we established mouse model by which we can address the contribution of TCR repertoire for tissue specificity of autoimmune disease. Besides, we found that restriction of TCR repertoire affected degree of autoimmune inflammation in a tissue-specific manner.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、組織特異的な自己免疫疾患発祥の原因が組織特異的なTregクローンの欠損とそれに紐づく組織特異的な自己反応性Tconvクローンの増加によるのかを検証できるマウスモデルを確立した。さらに、Tregの分化に重要な役割を果たす転写因子Foxp3の変異と抗原認識に関わるTCRレパトアの制限が合間って組織特異的に炎症を増悪させることを示した。これまでのゲノム医学研究により免疫応答を抑制するTreg関連遺伝子と抗原提示に関わるHLA遺伝子の一塩基多型が自己免疫疾患の発症と関連があることが示唆されてきたが、本研究でその分子機構に迫ることのできるマウスモデルを確立できたと考えている。
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Report
(3 results)
Research Products
(9 results)
