| 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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| 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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