期刊
NATURE NEUROSCIENCE
卷 25, 期 11, 页码 1446-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41593-022-01183-6
关键词
-
资金
- German Research Foundation (DFG) [SI/746 15-1, TRR 128-2, 408885537-TRR 274, EXC2145, ID390857198]
- Human Frontier Science Program
- ERC-ADG [101019594]
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Chan-Zuckerberg Initiative grant
- China Scholarship Council (CSC) fellowship program
- Else Kroner-Fresenius-Stiftung grant
- European Research Council (ERC) [101019594] Funding Source: European Research Council (ERC)
This study identified age-related alterations of oligodendrocyte cell state in aging murine white matter and found interferon (IFN)-responsive oligodendrocytes in proximity to CD8(+) T cells. Functional lymphocytes were shown to influence the number of IFN-responsive oligodendrocytes, with T-cell checkpoint inhibition exacerbating the aging response.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据