CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging.
Nat Neurosci
; 25(11): 1446-1457, 2022 11.
Article
in En
| MEDLINE
| ID: mdl-36280798
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Microglia
/
White Matter
Limits:
Animals
Language:
En
Journal:
Nat Neurosci
Journal subject:
NEUROLOGIA
Year:
2022
Document type:
Article
Affiliation country:
Alemania