Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Outline of Final Research Achievements |
We have demonstrated that NR4A2 influences Th17 differentiation and controls pathogenic Th17 responses in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. The prolonged NR4A2 expression in the central nervous system (CNS) is induced by a particular populations of inflammatory myeloid cells (IMC) isolated from the CNS during EAE and drive differentiation of Th17 cells. EAE symptoms in NR4A2cKO mice are greatly reduced concomitant with reduced infiltration of such IMC. Intriguingly, a late/chronic disease irrelevant of NR4A2-mediated Th17 responses emerged in those animals. A unique CD4+ T cell subset accumulated in CNS shows a typical pathogenic property. A specific marker gene upregulated in this Th cell subset is identified. Treatment with siRNA in vivo suppressed the late/chronic symptoms of EAE. Strikingly, human counterpart of this Th cell subset is remarkably increased in the peripheral blood from a particular subtype of MS patients.
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