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

Kaya, Tugberk; Mattugini, Nicola; Liu, Lu; Ji, Hao; Cantuti-Castelvetri, Ludovico; Wu, Jianping; Schifferer, Martina; Groh, Janos; Martini, Rudolf; Besson-Girard, Simon; Kaji, Seiji; Liesz, Arthur; Gökce, ÖzgÜn und Simons, Mikael (2022): CD8(+) T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging. In: Nature Neuroscience, Bd. 25, Nr. 11: S. 1446-1457

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1097-6256
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 408885537
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 213904703