| Project/Area Number |
15K10987
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊関 憲 福島県立医科大学, 医学部, 教授 (70332921)
関亦 明子 山形大学, 医学部, 准教授 (50321823)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 炎症制御 / 遺伝子発現 / サイトカイン / クロマチン構造 / エピジェネティクス / エピゲノム編集 / シス調節領域 / 転写因子 |
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| Outline of Final Research Achievements |
IL-22 is a cytokine that plays a pivotal role in regulating tissue homeostasis at barrier surfaces. Currently, the molecular mechanisms regulating Il22 gene expression are still unclear. Here, we have identified a crucial cis-regulatory element (CNS-32). We demonstrated that CNS-32 acts as an enhancer in reporter assays and contains binding motifs for Runx1 and RORγt. Mutation of these motifs significantly abrogated the reporter activity, suggesting a role for both factors in the control of enhancer-mediated Il22 expression. Overexpression of Runx1 promoted IL-22 production by inducing RORγt and IL-23 receptor, all critical to Th22 cell induction. Although Runx1 alone enhanced IL-22 production in Th22 cells, it was further enhanced in the presence of RORγt. Collectively, our results suggest that IL-22 production is controlled by a regulatory circuit in which Runx1 induces RORγt and then partners with RORγt to direct Il22 expression through their targeting of the Il22 enhancer.
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