TY - JOUR
T1 - CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging
AU - Kaya, Tuğberk
AU - Mattugini, Nicola
AU - Liu, Lu
AU - Ji, Hao
AU - Cantuti-Castelvetri, Ludovico
AU - Wu, Jianping
AU - Schifferer, Martina
AU - Groh, Janos
AU - Martini, Rudolf
AU - Besson-Girard, Simon
AU - Kaji, Seiji
AU - Liesz, Arthur
AU - Gokce, Ozgun
AU - Simons, Mikael
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85140457119&partnerID=8YFLogxK
U2 - 10.1038/s41593-022-01183-6
DO - 10.1038/s41593-022-01183-6
M3 - Article
C2 - 36280798
AN - SCOPUS:85140457119
SN - 1097-6256
VL - 25
SP - 1446
EP - 1457
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 11
ER -