德国慕尼黑路德维希·马克西米兰大学Mikael Simons和Ozgun Gokce共同合作近期取得重要工作进展，他们研究发现CD8⁺ T细胞在白质衰老过程中诱导干扰素反应性少突胶质细胞和小胶质细胞。相关论文2022年10月24日在线发表于《自然—神经科学》杂志上。

研究人员发现衰老小鼠白质中少突胶质细胞状态的年龄相关改变，和总少突胶质细胞密度的降低。使用单细胞RNA测序，研究人员确定干扰素（IFN）反应性少突胶质细胞在衰老白质中与CD8⁺ T细胞相邻定位。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损失，而T细胞检查点的抑制则恶化了衰老反应。

此外，研究人员在老化白质的CD8⁺ T细胞附近发现了一个淋巴细胞依赖性、IFN反应性的小胶质细胞亚群。总之，这些证据表明，CD8⁺ T细胞诱导的、IFN反应性的少突胶质细胞和小胶质细胞是白质老化的重要修饰因素。

据介绍，神经系统老化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。

附：英文原文

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

Author: Kaya, Tuberk, 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

Issue&Volume: 2022-10-24

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.

DOI: 10.1038/s41593-022-01183-6

Source: https://www.nature.com/articles/s41593-022-01183-6