艾伦免疫学研究所Claire E. Gustafson小组发现了多组学分析揭示健康成人年龄相关免疫动力学。这一研究成果于2025年10月29日发表在国际顶尖学术期刊《自然》上。

为了更好地了解其进展，研究组使用单细胞RNA测序、蛋白质组学和流式细胞术对300多名健康成人（25 - 90岁）的外周免疫进行了分析，对96名接种季节性流感疫苗的成年人进行了为期2年的纵向随访。由此产生的资源生成了一个单细胞RNA测序数据集，其中包含1600多万个外周血单核细胞，以及我们人类免疫健康图谱中的71个免疫细胞亚群，使我们能够研究免疫细胞组成和状态如何随着年龄、慢性病毒感染和疫苗接种而变化。

根据这些数据，该课题组证明了T细胞亚群随年龄的非线性转录重编程，而不是由全身性炎症或慢性巨细胞病毒感染驱动。这种与年龄相关的重编程导致记忆T细胞中功能性T辅助2 （T_H2）细胞偏倚，这与流感疫苗中对高度增强抗原的B细胞反应失调有关。总的来说，这项研究揭示了在老年之前发生的免疫衰老过程的独特特征，并为与年龄相关的免疫调节提供了新的靶点。课题组人员在https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/上提供了探索这种广泛的人类免疫健康抵抗的互动工具。

据了解，免疫的产生和维持是一个依赖于年龄的动态过程。

附：英文原文

Title: Multi-omic profiling reveals age-related immune dynamics in healthy adults

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

Issue&Volume: 2025-10-29

Abstract: The generation and maintenance of immunity is a dynamic process that is dependent on age1,2,3. Here, to better understand its progression, we profiled peripheral immunity in more than 300 healthy adults (25 to 90years of age) using single-cell RNA sequencing, proteomics and flow cytometry, following 96 adults longitudinally across 2 years with seasonal influenza vaccination. The resulting resource generated a single-cell RNA-sequencing dataset of more than 16 million peripheral blood mononuclear cells with 71 immune cell subsets from our Human Immune Health Atlas and enabled us to interrogate how immune cell composition and states shift with age, chronic viral infection and vaccination. From these data, we demonstrate robust, non-linear transcriptional reprogramming in T cell subsets with age that is not driven by systemic inflammation or chronic cytomegalovirus infection. This age-related reprogramming led to a functional T helper 2 (TH2) cell bias in memory T cells that is linked to dysregulated B cell responses against highly boosted antigens in influenza vaccines. Collectively, this study reveals unique features of the immune ageing process that occur prior to advanced age and provides novel targets for age-related immune modulation. We provide interactive tools for exploring this extensive human immune health resource at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/.

DOI: 10.1038/s41586-025-09686-5

Source: https://www.nature.com/articles/s41586-025-09686-5