Development of novel immunotherapies using retinoid X agonists
| Project/Area Number |
23590317
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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 |
General pharmacology
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | RXRアゴニスト / Th17 / 制御性T細胞 / レチノイン酸 / EAE / RXRシグナル / RXR |
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| Research Abstract |
Retinoic acid (RA) enhances TGF-beta-dependent differentiation of Foxp3+ inducible regulatory T cells (iTreg) and inhibits Th17 differentiation by binding to the retinoic acid receptor (RAR). It remained unclear if RXR-mediated stimulation affected the iTreg and Th17 differentiation. We found here that the RXR agonists augmented the ability of RA or the RAR agonist to enhance CD4+CD25- T cells to acquire Foxp3 expression and suppressive function.
RXR agonists alone suppressed ROR-gamma-t mRNA and IL-17 expression. The combination of an RXR agonist and RA additively suppressed Th17 differentiation when the concentration of RA was low. Accordingly, continuous treatment with an RXR agonist ameliorated experimental autoimmune encephalomyelitis. These results suggest that RXR stimulation enhances RAR-dependent and independent modulation of Foxp3+ iTreg and Th17 differentiation, respectively.
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Retinoid X receptor agonists modulate Foxp3+ regulatory T cell and Th17 cell with differential dependence on retinoic acid receptor activation2013
Author(s)
Takeuchi, H., Yokota-Nakatsuma, A., Ohoka, Y., Kagechika, H., Kato, C., Song S.Y., Iwata M.
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Journal Title
J Immunol
Volume: 191
Pages: 3725-3733
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[Presentation] haracterization of the role of retinoid X receptor signaling in the differentiation of Th17
Author(s)
Takeuchi, H., Yokota-Nakatsuma, A., Ohoka, Y., Kagechika, H., Song, S-Y., Iwata, M.
Organizer
第42回日本免疫学会
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