Analyses of cellular component involved in heterogeneous inflammatory pathogenesis of autoimmne diseases in the CNS

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590108
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: OKI SHINJI 独立行政法人国立精神・神経医療研究センター, 神経研究所 疾病研究第六部, 室長 (50260328)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 自己免疫疾患 / 多発性硬化症 / Th17細胞 / NR4A2 / 細胞間相互作用 / 炎症性ミエロイド細胞 / 病態多様性 / バイオマーカー

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.

Free Research Field

免疫