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Brain Environment: Glia in neurological disease

開催日 2014/9/12
時間 15:00 - 17:00
会場 Room E(301)
Chairperson(s) 小峯 起 / Okiru Komine (名古屋大学 環境医学研究所 病態神経科学分野 / Department of Neuroscience and Pathobiology, Research Institute for Environmental Medicine, Nagoya University, Japan)
村松 里衣子 / Rieko Muramatsu (大阪大学大学院医学系研究科 分子神経科学JST-さきがけ / Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Japan Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology )

The role of the infiltrating immune cells in amyotrophic lateral sclerosis

  • S2-E-2-5
  • 小峯 起 / Okiru Komine:1 山下 博史 / Hirofumi Yamashita:2 藤森 典子 / Noriko Fujimori-Tonou:1 森脇 康博 / Yasuhiro Moriwaki:3 三澤 日出巳 / Hidemi Misawa:3 山中 宏二 / Koji Yamanaka:1 
  • 1:名古屋大・環境医・病態神経科学 / Dept Neurosci and Pathobiol, Res Inst of Env Med, Nagoya Univ, Aichi, Japan 2:京都大・医・神経内科 / Dept Neurol, Kyoto Univ, Kyoto, Japan 3:慶應大・薬・薬理 / Dept Pharmacol, Facul of Pharma, Keio Univ, Tokyo, Japan 

Infiltration of immune cells was observed in the spinal cord of both human amyotrophic lateral sclerosis (ALS) patients and mutant SOD1 (mSOD1) mice, used as an ALS model. Recent studies demonstrated that infiltrating T-lymphocyte contributed to disease progression by regulating microglial activation in mSOD1 mice. However, the characterization of infiltrating immune cells and the detailed functions of these cells in ALS were not fully investigated. Meanwhile, in Alzheimer disease, infiltrating monocytes were shown to be involved in the clearance of amyloid-beta. Therefore, accumulating evidence suggests that immune cells actively contribute to disease processes of neurodegenerative diseases.
To identify the subset of infiltrating immune cells, we performed flow cytometric analyses in the spinal cord of mSOD1 mice. Contrasting to the prior reports, we found that infiltrating immune cells are mainly CD8+ T-lymphocytes, natural killer T-lymphocytes, and natural killer cells that have cytotoxic functions. In addition, our study revealed that the defect of TRIF-pathway, which is one of the Toll-like receptor signaling pathways, in mSOD1 mice resulted in the acceleration of disease progression accompanied by the fewer infiltration of these immune cells and the increase in number of aberrantly activated glia in comparison to mSOD1 mice. Thus, we hypothethized that these cytotoxic immune cells have a beneficial role in protecting motor neurons through inducing apoptosis to the aberrantly activated glia for elimination. Indeed, the decrease in number of apoptotic aberrantly activated glia was observed in TRIF-deficient mSOD1 mice in comparison to mSOD1 mice. To date, it has never been validated how activated glia is processed for terminating inflammatory response. The novel function of infiltrating immune cells in the neurodegenerative diseases will be discussed.

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