CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging
2022-11 | journal article
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CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging
Kaya, T.; Mattugini, N.; Liu, L.; Ji, H.; Cantuti-Castelvetri, L. ; Wu, J. & Schifferer, M. et al. (2022)
Nature Neuroscience, 25(11) pp. 1446-1457. DOI: https://doi.org/10.1038/s41593-022-01183-6
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Details
- Authors
- Kaya, Tuğberk; Mattugini, Nicola; Liu, Lu; Ji, Hao; Cantuti-Castelvetri, Ludovico ; Wu, Jianping; Schifferer, Martina; Groh, Janos; Martini, Rudolf; Besson-Girard, Simon; Kaji, Seiji; Liesz, Arthur ; Gokce, Ozgun ; Simons, Mikael
- 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.
- Issue Date
- November-2022
- Journal
- Nature Neuroscience
- Project
- TRR 274: Checkpoints of Central Nervous System Recovery
TRR 274 | Z02: Genomics and Bioinformatics Platform - Working Group
- RG Cantuti
RG Gokce (Systems Neuroscience – Cell Diversity)
RG Liesz (Stroke-Immunology)
RG Schifferer
RG Simons (The Biology of Glia in Development and Disease) - ISSN
- 1097-6256
- eISSN
- 1546-1726
- Language
- English