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Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630119 | PMC |
| http://dx.doi.org/10.1038/s41593-022-01183-6 | DOI Listing |
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