Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain.
Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain.
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DOI：
10.34133/research.0287
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Shi L
中科院分区：
文献类型：
--
作者：
Lu J;Li H;Zhang G;Yang F;Zhang X;Ping A;Xu Z;Gu Y;Wang R;Ying D;Liu J;Zhang J;Shi L
免疫衰老是指衰老带来的免疫系统多方面的深刻改变，对其所表现的疾病的病理生理过程产生复杂的影响。结合单细胞RNA测序、飞行时间细胞计数和各种免疫学检测，我们研究了老年小鼠外周血中免疫衰老的特征及其对缺血性脑卒中后脑免疫环境的影响。我们的结果揭示了免疫衰老的一些特征。我们观察到中性粒细胞计数增加，同时中性粒细胞衰老加速，其特征是衰老相关标记物（如 CD62L）的表达改变以及中性粒细胞介导的免疫功能的相应变化。老年小鼠的单核细胞/巨噬细胞表现出增强的抗原呈递能力。 T 细胞特征从初始状态转变为效应或记忆状态，辅助性 T 细胞 1 和辅助性 T 17 细胞亚群明显增加，CD4 T 细胞中的调节性 T 细胞激活增加。此外，Klra 标记的调节性 CD8 T 细胞随着衰老而减少，而耗尽样 CD8 T 细胞的亚群则扩张，保留了有效的免疫刺激和促炎功能。至关重要的是，这些固有的差异不仅持续存在，而且在中风后的缺血半球内进一步放大。总之，我们对外周免疫衰老关键属性的全面见解不仅为理解缺血性中风而且为理解其他与年龄相关的疾病提供了重要的理论基础。
Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and various immunological assays, we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke. Our results revealed some features of immunosenescence. We observed an increase in neutrophil counts, concurrent with accelerated neutrophil aging, characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions. Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities. T cell profiles shifted from naive to effector or memory states, with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells. Furthermore, regulatory CD8 T cells marked by Klra decreased with aging, while a subpopulation of exhausted-like CD8 T cells expanded, retaining potent immunostimulatory and proinflammatory functions. Critically, these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke. In summary, our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.
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