少突胶质细胞
小胶质细胞
白质
生物
CD8型
神经科学
干扰素
细胞生物学
中枢神经系统
髓鞘
免疫学
炎症
免疫系统
医学
放射科
磁共振成像
作者
Tuğberk Kaya,Nicola Mattugini,Lu Liu,Hao Ji,Ludovico Cantuti-Castelvetri,Jianping Weng,Martina Schifferer,Janos Groh,Rudolf Martini,Simon Besson-Girard,Shunsuke Kaji,Arthur Liesz,Özgün Gökçe,Mikael Simons
标识
DOI:10.1038/s41593-022-01183-6
摘要
A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. In the present study, we found age-related alterations of oligodendrocyte cell state with a reduction in total oligodendrocyte density in aging murine white matter. Using single-cell RNA-sequencing, we identified interferon (IFN)-responsive oligodendrocytes, which localize in proximity to CD8+ T cells in aging white matter. Absence of functional lymphocytes decreased the number of IFN-responsive oligodendrocytes and rescued oligodendrocyte loss, whereas T-cell checkpoint inhibition worsened the aging response. In addition, we identified a subpopulation of lymphocyte-dependent, IFN-responsive microglia in the vicinity of the CD8+ T cells in aging white matter. In summary, we provide evidence that CD8+ T-cell-induced, IFN-responsive oligodendrocytes and microglia are important modifiers of white matter aging.
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