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CD8 T 细胞在白质老化中诱导干扰素反应性少突胶质细胞和小胶质细胞。

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

机构信息

Institute for Stroke and Dementia Research, University Hospital of Munich, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.

Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.

出版信息

Nat Neurosci. 2022 Nov;25(11):1446-1457. doi: 10.1038/s41593-022-01183-6. Epub 2022 Oct 24.

DOI:10.1038/s41593-022-01183-6
PMID:36280798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9630119/
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.

摘要

神经系统衰老的一个标志是白质体积和功能的下降，但导致白质病变的潜在机制尚不清楚。在本研究中，我们发现衰老小鼠白质中少突胶质细胞状态随年龄相关改变，总少突胶质细胞密度降低。通过单细胞 RNA 测序，我们鉴定了干扰素 (IFN) 反应性少突胶质细胞，其在衰老白质中定位于 CD8 T 细胞附近。功能性淋巴细胞的缺失减少了 IFN 反应性少突胶质细胞的数量，并挽救了少突胶质细胞的丢失，而 T 细胞检查点抑制则加重了衰老反应。此外，我们还在衰老白质中 CD8 T 细胞附近鉴定出了一群依赖淋巴细胞的 IFN 反应性小胶质细胞。总之，我们提供的证据表明，CD8 T 细胞诱导的 IFN 反应性少突胶质细胞和小胶质细胞是白质衰老的重要调节因子。

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