| Project/Area Number |
15K09551
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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 |
Collagenous pathology/Allergology
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| Research Institution | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 寛容型樹状細胞 / 自己免疫疾患 / 制御性T細胞 |
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| Outline of Final Research Achievements |
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3, rapamycin (Rapa), IL-10, TGF-beta, and a combination of peroxisome proliferator-activated receptor gamma agonist and retinoic acid. PKCI-, TGF-beta-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with Sjogren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトのtDCsの治療効果については、欧州や米国を中心にI型糖尿病，関節リウマチ, クローン病、多発性硬化症に対して臨床試験が進められている。これらの試験において、いずれも安全性は確認されており、効果もあることが報告されている。これらの臨床研究で用いているtDCsは様々な方法で誘導したtDCsを用いているが、我々はPKCI-tDCsが最も良いことを明らかにした。PKCI-tDCsは自己免疫疾患における抗原特異的免疫抑制療法の有力なツールになることが期待される。
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