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T cells induce interferon-responsive oligodendrocytes during white matter aging

Kaya, T.; Mattugini, N.; Liu, L.; Ji, H.; Besson-Girard, S.; Kaji, S.; Liesz, A.; Gokce, O.; Simons, M.

2022-03-27 neuroscience
10.1101/2022.03.26.485917 bioRxiv
Show 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. Here, we found age-related alterations of oligodendrocytes with a reduction of total oligodendrocyte density in the aging murine white matter. Using single-cell RNA sequencing, we identify interferon-responsive oligodendrocytes, which localize in proximity of CD8+ T cells in the aging white matter. Absence of functional lymphocytes decreased oligodendrocyte reactivity and rescued oligodendrocyte loss, while T-cell checkpoint inhibition worsened the aging affect. In summary, we provide evidence that T cells induced interferon-responsive oligodendrocytes are important modifiers of white matter aging.

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