纵向多组学免疫分析揭示健康成年人与年龄相关的免疫细胞动态变化

Qiuyu Gong, Mehul Sharma, Emma L. Kuan, Marla C. Glass, Aishwarya Chander, Mansi Singh, Lucas T. Graybuck, Zachary J. Thomson, Christian M. LaFrance, Samir Rachid Zaim, Tao Peng, Lauren Y. Okada, Palak C. Genge, Katherine E. Henderson, Elisabeth M. Dornisch, Erik D. Layton, Peter J. Wittig, Alexander T. Heubeck, Nelson M. Mukuka, Julian Reading, Charles R. Roll, Veronica Hernandez, Vaishnavi Parthasarathy, Tyanna J. Stuckey, Blessing Musgrove, Elliott Swanson, Cara Lord, Morgan D.A. Weiss, Cole G. Phalen, Regina R. Mettey, Kevin J. Lee, John B. Johanneson, Erin K. Kawelo, Jessica Garber, Upaasana Krishnan, Megan Smithmeyer, E. John Wherry, Laura Vella, Sarah E. Henrickson, Mackenzie S. Kopp, Adam K. Savage, Lynne A. Becker, Paul Meijer, Ernest M. Coffey, Jorg J. Goronzy, Cate Speake, Thomas F. Bumol, Ananda W. Goldrath, Troy R. Torgerson, Xiao-jun Li, Peter J. Skene, Jane H. Buckner, Claire E. Gustafson
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引用次数: 0

摘要

保护性免疫力的产生和维持是宿主与环境之间受年龄影响的动态相互作用。了解健康免疫系统在人的一生中发生的根本性变化,对于开发针对与年龄相关的易感染性和疾病的干预措施至关重要。在这里,我们利用多组学分析(scRNA-seq、蛋白质组学、流式细胞术)研究了 300 多名健康成年人的人体外周免疫系统,其中 96 名年轻人和老年人接受了为期两年的随访,每年接种一次疫苗。由此获得的资源包括 1,600 万 PBMCs 的 scRNA-seq 数据集,对我们新的免疫健康图谱中的 71 个免疫细胞亚群进行了检测。通过这项研究,我们可以深入了解免疫细胞在平衡状态、疫苗干扰以及不同年龄段的组成和转录状态。我们发现,与其他免疫细胞相比,T 细胞特异性地积累了与年龄相关的转录变化,这与炎症和慢性干扰无关。此外,记忆性 B 细胞对疫苗接种的反应受损与老年人记忆性 CD4 T 细胞的 Th2 类状态转变有关,揭示了人类健康衰老过程中免疫失调的可能机制。https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ 上提供了这一广泛的资源和一套探索工具,以提高数据的可访问性,并进一步了解不同年龄段的免疫健康状况。
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Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults
The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination. The resulting resource includes scRNA-seq datasets of >16 million PBMCs, interrogating 71 immune cell subsets from our new Immune Health Atlas. This study allows unique insights into the composition and transcriptional state of immune cells at homeostasis, with vaccine perturbation, and across age. We find that T cells specifically accumulate age-related transcriptional changes more than other immune cells, independent from inflammation and chronic perturbation. Moreover, impaired memory B cell responses to vaccination are linked to a Th2-like state shift in older adults' memory CD4 T cells, revealing possible mechanisms of immune dysregulation during healthy human aging. This extensive resource is provided with a suite of exploration tools at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ to enhance data accessibility and further the understanding of immune health across age.
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