| Project/Area Number |
24591464
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Ehime University |
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Principal Investigator |
HASEGAWA Hitoshi 愛媛大学, 医学(系)研究科(研究院), 准教授 (40164826)
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| Co-Investigator(Renkei-kenkyūsha) |
SUEMORI Koichiro 愛媛大学, 医学部附属病院, 助教 (80571083)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | dendritic cells / regulatory T cells / protein kinase C / 寛容型樹状細胞 / 制御性T細胞 / 制御性Ｔ細胞 |
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| Outline of Final Research Achievements |
Tolerogenic dendritic cells (tDCs) are a promising tool for cellular therapy for allergy and autoimmunity. From libraries of bioactive lipids, nuclear receptor ligands, and kinase inhibitors, we screened conventional protein kinase C inhibitors (PKCIs) with strong tolerogenic potential. The PKCI-treated DCs had a semi-mature phenotype, showing high production of IL-10, and efficiently induced IL-10-producing T cells and functional Foxp3+ regulatory T cells from naive CD4+ T cells, thus eliciting a strong immunosuppressive function. They also showed CCR7 expression and sufficient capacity for migration toward CCR7 ligands. In addition, PKCI-treated DCs were highly stable when exposed to inflammatory stimuli such as proinflammatory cytokines or LPS. Moreover, PKCI-treated mouse DCs that had properties similar to PKCI-treated human DCs prevented graft-vs-host disease (GVHD) in a murine model of acute GVHD. Conventional PKCI-treated DCs may be useful for tolerance-inducing therapy.
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