CD8(+) T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging.
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BiBTeXA 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.
SEEK ID: http://lmmeisd-2.srv.mwn.de/publications/2
PubMed ID: 36280798
Projects: Published Datasets
Publication type: Journal
Journal: Nat Neurosci
Citation: Nat Neurosci. 2022 Nov;25(11):1446-1457. doi: 10.1038/s41593-022-01183-6. Epub 2022 Oct 24.
Date Published: 26th Oct 2022
Registered Mode: by PubMed ID
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Created: 27th Jun 2024 at 12:02
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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 ...
Submitter: Rainer Malik
Investigation: Transcriptomics (Published)
