| Project/Area Number |
21590531
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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 | Kyoto University |
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Principal Investigator |
IKUTA Koichi 京都大学, ウイルス研究所, 教授 (90193177)
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| Co-Investigator(Kenkyū-buntansha) |
TANI-ICHI Shizue 京都大学, ウイルス研究所, 助教 (50432331)
HARA Takahiro 京都大学, ウイルス研究所, 助教 (90512301)
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| Co-Investigator(Renkei-kenkyūsha) |
IMAI Kumiko 京都大学, ウイルス研究所, 教務補佐員
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | サイトカイン / IL-7 / ストローマ細胞 / 小腸上皮内リンパ球 / γδ T細胞 / インターロイキン7 / リンパ組織 / 遺伝子改変マウス / 胸腺 / NKT細胞 / 胸腺上皮細胞 / GFP / T細胞 |
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| Research Abstract |
IL-7 is an essential cytokine for lymphocyte development and survival produced by mesenchymal and epithelial cells in lymphoid organs. However, little is known about the precise nature and distribution of IL-7-expressing cells in vivo. To address this question, we established IL-7-GFP knock-in mice. We found that GFP is expressed in bone marrow stromal cells, thymic epithelial cells(TECs), fibroblastic reticular cells(FRCs) and lymphatic endothelial cells in lymph nodes, and intestinal epithelial cells. After induction of acute colitis with DSS, GFP expression was elevated in the intestinal epithelial cells. Thus, the IL-7-GFP knock-in mouse reveals unreported types of IL-7-expressing cells and provides a powerful tool to analyze the IL-7-niche in the lymphoid organs under physiological and pathological conditions. We next established IL-7-floxed mice and crossed with FoxN1-Cre transgenic(Tg) mice to obtain the conditional knockout mice deficient in IL-7 production from TECs. FoxN1-Cre
… More
IL-7flox/flox mice showed severely reduced numbers of total andγδT cells in the thymus. These results suggested that IL-7 produced by TECs plays a major role in proliferation, survival, and maturation of thymocytes. In small intestine, cell numbers ofγδIELs were significantly reduced in FoxN1-Cre IL-7flox/flox mice, suggesting that IL-7 produced in the thymus is essential forγδIEL development. Thus, this study presents strong evidence for the thymic originγδIELs. We next crossed IL-7-floxed mice with albumin promoter-driven Cre(Alb-Cre) Tg mice to establish conditional knockout of IL-7 in hepatocytes. We found that NKT and T cells were moderately decreased in adultliver of IL-7f/f Alb-Cre mice and that B cell development was impaired in perinatal liver of IL-7f/f Alb-Cre mice. This study demonstrates that hepatocyte-derived IL-7 plays an indispensable role in maintenance of NKT and T cells in adult liver and development of B cells in fetal liver and suggests that hepatocytes provide a unique IL-7 niche for intrahepatic lymphocytes. Less
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