グリア前駆細胞由来エクソソーム中のmiR-155-5pが脱髄部位ミクログリアの極性転換に及ぼす効果
小野健治; 大橋和哉; 鈴木弘美; 澤田 誠
第46回日本神経科学大会 2023年08月 ポスター発表 仙台
When demyelinated NG2-ChR2 mice, which express channelrhodopsin-2 (ChR2) in NG2-positive glial progenitor cells, are exposed to blue light, not only some NG2-positive glial progenitor cells are differentiated into oligodendrocytes, but also accumulation of CD206 (an M2 marker)-positive microglia are found around the demyelinated area. Although these contribute to recovery of demyelinating symptoms, it remains unclear how the microglial M1 to M2 polarity switch occurs. In this study, we examined the effect of exosomal miRNAs from glial progenitor cells in microglial polarization at the demyelinated area since exosomes play important roles in intercellular communications via miRNAs. In miRNA analysis of exosomes derived from OS3ChR2, a ChR2-expressing NG2 glial progenitor cell line, in the presence (BL) or absence (N) of blue light exposure, inflammatory and M1 polarization-related miRNAs such as miR-155-5p, miR-743b-3p, and miR-291a-3p were decreased in exosomes from OS3ChR2 BL. In microglia treated with exosomes from OS3ChR2 BL, inflammatory-related mRNA expressions such as IL-1, TNF, and iNOS (an M1 marker) and CD206 mRNA expression were not altered as compared to microglia without exosome treatment. On the other hand, in microglia treated with exosomes from OS3ChR2 N, inflammatory-related mRNA expressions were increased and CD206 mRNA expression was decreased. Many iNOS-positive microglia and few CD206-positive microglia were found at corpus callosum of demyelinated mice. When exosomes from OS3ChR2 N were injected into the corpus callosum, iNOS-positive microglia were increased. When exosomes from OS3ChR2 BL were injected, iNOS-positive microglia were decreased and CD206-positive microglia were increased around the demyelinated area. Further, when miR-155-5p inhibitor was injected into the corpus callosum of demyelinated mice, iNOS-positive microglia were decreased and CD206-positive microglia were increased. These indicate that differentiated glial progenitor cells have a potential to control microglial polarity via exosomes. In addition, these suggested that glial progenitor cells would communicate to microglia with exosomal miRNA such as miR-155-5p in the demyelinated mice.