Suppression of experimental autoimmune encephalomyelitis by anti-midkine RNA aptamers.
| Project/Area Number |
22790816
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Nagoya University |
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Principal Investigator |
SONOBE Yoshifumi 名古屋大学, 大学院・医学系研究科, COE特任助教 (20534845)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 多発性硬化症 / 神経免疫 / 制御性T細胞 / 樹状細胞 / 細胞内シグナリング |
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| Research Abstract |
In this study, we investigated how midkine(MK) decreased regulatory CD4^+CD25^+Foxp^<3+> T cells(Tregs) in experimental autoimmune encephalomyelitis(EAE). DCreg expressed produced significantly less IL-12 compared with conventional DCs. However, MK induced IL-12 production by reducing phosphorylated STAT3 levels via src homology region 2 domain. containing phosphatase-2 in DCreg. Inhibiting MK activity with anti-MK RNA aptamers, which binds to the targeted protein to suppress the function of the protein, increased the numbers of CD11c^<low> CD45RB^+DCs and Treg in the draining lymph nodes, and suppressed the severity of EAE, an animal model of multiple sclerosis(MS). Our results also demonstrated that MK was produced by inflammatory cells, and in particular CD4^+T cells under inflammatory conditions. Taken together, these results suggest that MK aggravates EAE by suppressing DCreg development, thereby impairing the Treg population. Thus, MK is a promising therapeutic target for various autoimmune diseases.
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease.2011
Author(s)
Takeuchi H, Mizoguchi H, Doi Y, Jin S, Noda M, Liang J, Li H, Zhou Y, Mori R, Yasuoka S, Li E, Parajuli B, Kawanokuchi J, Sonobe Y, Sato J, Yamanaka K, Sobue G, Mizuno T, Suzumura A
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Peer Reviewed
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