ミクログリアの適切な分布と増殖に機械受容性チャネルPiezo1が関与する

抄録

The immune system of the central nervous system (CNS) consists primarily of innate immune cells. As the tissue-resident macrophages, microglia, which are distributed at equal intervals in the CNS parenchyma, play a pivotal role in the maintenance of tissue homeostasis. During the CNS disease, on the other hand, microglia increase in number and exert their proper function. However, the molecular mechanism by which microglia control their cellular density during homeostasis and perturbation remains unknown. In the present study, we investigated the role of Piezo1, a mechanosensitive ion channel, in the regulation of microglia density. In the brains of mice with specific deletion of Piezo1 in myeloid cells including microglia (Piezo1-KO), the density and the morphology of microglia didn’t differ from those in wild-type controls. However, after pharmacological depletion of microglia with BLZ945, an inhibitor of colony-stimulating factor 1 receptor, Piezo1-KO microglia showed impaired repopulation capacity with less proliferation rate, leading to lower cell density in the brain. Together, these findings suggest that Piezo1 is involved in regulating proper density of microglia following repopulation.