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Roles for innate immunity in neurological and psychiatric disorders

開催日 2014/9/12
時間 17:10 - 19:10
会場 Room E(301)
Chairperson(s) 山中 宏二 / Koji Yamanaka (名古屋大学環境医学研究所病態神経科学分野 / Research Institute of Environmental Medicine, Nagoya University, Japan)
古屋敷 智之 / Tomoyuki Furuyashiki (神戸大学大学院医学研究科薬理学 / Division of Pharmacology, Kobe University Graduate School of Medicine, Japan)

The role of innate immune system in sporadic and inherited amyotrophic lateral sclerosis

  • S2-E-3-1
  • 山中 宏二 / Koji Yamanaka:1 
  • 1:名古屋大学・環境医学研究所 / Nagoya University, Research Institute of Environmental Medicine, Japan 

Increasing evidence suggests involvement of immune system in the pathomechanism of neurodegenerative diseases, while the roles of innate immune system in amyotrophic lateral sclerosis (ALS), an adult motor neuron disease are not clarified. Our previous study established the roles of microglia and astrocytes in disease progression of mutant SOD1 mice, inherited ALS model, through cell-type specific deletion of mutant SOD1 in mice.
Microarray analysis using our cell-type specific transcriptome identified significant number of genes involved in innate immune system enriched within microglia in the spinal cords of symptomatic mutant SOD1 mice and sporadic ALS patients in common. The inhibition of innate immune system by eliminating TRIF (TIR domain-containing adaptor inducing IFN-β), an essential adaptor for Toll-like receptor signaling, from SOD1G93A mice significantly accelerated disease progression with defective chemokines in the spinal cord. In contrast, blockade of MyD88-dependent innate immune pathway showed marginal effect on the onset and survival time of ALS mice. Furthermore, TRIF-deficient mutant SOD1 mice exhibited fewer infiltrating immune cells with accumulation of aberrantly activated astrocytes in the spinal cord. Our results provide novel evidence that TRIF dependent-innate immune activation of microglia plays an important role in slowing disease progression likely through regulating pro-inflammatory chemokines, which recruit immune cells for eliminating aberrant astrocyte to protect motor neurons.

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