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Cited by 224Neuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanisms

CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging

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Kaya, Tuğberk, Mattugini, Nicola, Liu, Lu, Ji, Hao, Cantuti-Castelvetri, Ludovico, Wu, Jianping, Schifferer, Martina, Groh, Janos +6 more·2022·Nature Neuroscience
DOI 10.1038/s41593-022-01183-6PMC PMC9630119
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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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  • Loss of PLCγ2 enhances T cell mediated oligodendrocyte and microglia dyshomeostasis, which could explain the results showing that myelin lipids decrease in PLCγ2 KO mice.

    “perhaps loss of PLCγ2 enhances T cell mediated oligodendrocyte and microglia dyshomeostasis which could explain our results showing that myelin lipids decrease in PLCγ2 KO mice (Figure 3A–C).”

    From Multi-omics analyses reveal novel effects of PLCγ2 deficiency in the mouse brain (2023) · cites this paper as [43]

    The Results section reports that CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in aged white matter, and that mice lacking functional CD8+ T cells have less oligodendrocyte loss. It does not establish that loss of PLCγ2 enhances those T-cell-mediated changes. The decrease in myelin lipids is described in the citing sentence as the citing authors’ own result, not a finding attributed to this source. Page numbers were not available in our copy. (LLM, conf=0.87)

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References 74 · Cited by 224

Research works printed but not linked: 44

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Authors
Kaya, T., Mattugini, N., Liu, L., Ji, H., Cantuti-Castelvetri, L., Wu, J., Schifferer, M., Groh, J., Martini, R., Besson-Girard, S., Kaji, S., Liesz, A., Gokce, O., & Simons, M.
Affiliations
  • German Center for Neurodegenerative Diseases (DE)
  • LMU Klinikum (DE)
  • Universitätsklinikum Würzburg (DE)
Corresponding author
Simons, Mikael
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2022-10-24
Volume
25
Issue
11
Pages
1446-1457
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-022-01183-6
PMC
PMC9630119
OpenAlex
W4307233008
Cited by
224
References
74
Citations by year
2026: 62 · 2025: 55 · 2024: 65 · 2023: 39 · 2022: 3
FWCI
15.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DZNE Pub (publishedVersion, other-oa)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (acceptedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion)
Funders
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • Deutsche Forschungsgemeinschaft (EXC 2145, TRR-274, 390857198, TRR128-2, 101019594, 408885537)
  • Else Kröner-Fresenius-Stiftung
  • China Scholarship Council
  • Deutsches Zentrum für Neurodegenerative Erkrankungen
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
white matter aging, CD8+ T cells, oligodendrocyte loss, neuroinflammation, lymphocyte depletion, single-cell RNA sequencing
MeSH terms
Animals, Interferons, Oligodendroglia, Microglia, CD8-Positive T-Lymphocytes, Mice, White Matter

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