本研究では脊髄損傷時における免疫系と神経系との細胞間相互作用を解析した。脊髄損傷部位においては損傷後に免疫細胞の集積が見られ, この免疫系細胞の周辺にはOlig2陽性のオリゴデンドロサイト前駆細胞が集積することが明らかとなった。同時にオリゴデンドロサイト前駆細胞は正常時には増殖が非常に緩やかな細胞集団であるが損傷依存的に増殖が活性化することが明らかとなった。この機構の一端として本研究では細胞間シグナル伝達機構の一つして知られるNotchシグナルの活性化が関与していることが明らかとなった。
To unravel mechanistic insight in progression of spinal cord injury, I focused on the interaction between the immune system and the nervous system. I initially discovered activation of Sox2 exprssion in the injured site and,importantly, the Sox2-positive cells were surrounded by microglial cells. To further clarify the mechanism of Sox2 upregulation, we characterized the cells and found that these cells were oligodendrocyte precursor cells (OPCs). At the site of spinal cord injury, immune cell accumulation was observed after injury, and these immune cells expressed ligand for Notch signaling. Then, proliferation of OPCs was activated by Notch signaling. Furthermore, conditional knockout of RBP-J, an effector of Notch signaling, in OPCs resulted in defect in activation of OPCs, indicating that interaction between immune system and nervous system, which was mediated by Notch signaling is important for pathogenesis of spinal cord injury.
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