First Author | Kaya T | Year | 2022 |
Journal | Nat Neurosci | Volume | 25 |
Issue | 11 | Pages | 1446-1457 |
PubMed ID | 36280798 | Mgi Jnum | J:337595 |
Mgi Id | MGI:7486703 | Doi | 10.1038/s41593-022-01183-6 |
Citation | Kaya T, et al. (2022) CD8(+) T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging. Nat Neurosci 25(11):1446-1457 |
abstractText | 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. |