Nehar-Belaid Djamel, Thibodeau Asa, Eroglu Alper, Marches Radu, Eryilmaz Giray, Unutmaz Derya, Verschoor Chris P, Gu Jinghua, Balaji Uthra, Mejías Asunción, Pascual Virginia, Kuchel George A, Ramilo Octavio, Banchereau Jacques F, Ucar Duygu
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032 USA.
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, 171 77, Sweden.
bioRxiv. 2025 Jul 31:2025.07.28.667181. doi: 10.1101/2025.07.28.667181.
The human immune system undergoes continuous remodeling from infancy through old age, yet the timing and trajectory of these changes across the lifespan remain poorly defined. To address this, we profiled peripheral blood mononuclear cells from 95 healthy individuals (ages 2 months to 88 years), including infants (n=27), children (n=23), adults (n=18), and older adults (n=27) using scRNA-seq and snATAC-seq. MAIT and γδ T cells showed a "Rise and fall" pattern, which rise in childhood, peak in young adulthood, and decline with age. CD8 T cells were the most affected by aging with decreasing naïve T cells and increasing GzK CD8 T cells and TEMRA cells. Infants had lower myeloid/lymphoid ratio, with a distinct composition marked by increased frequencies of CD16 monocytes and plasmacytoid dendritic cells and reduced frequencies of CD14 monocytes and conventional DCs. Their adaptive immune compartment also displayed unique features, including constitutive interferon-stimulated gene expression in T and B cells, and an expanded SOX4 populations in naïve CD4, naïve CD8 and γδ T cells, comprising ~30% of the naïve T cell pool. SOX4 naïve CD4 T cells displayed a Th2 epigenetic signature. This map provides critical insights into human immune system dynamics across the lifespan, emphasizing unique features of the infant immune system.
人类免疫系统从婴儿期到老年期都在持续重塑，然而这些变化在整个生命周期中的时间和轨迹仍未明确界定。为了解决这个问题，我们使用单细胞RNA测序（scRNA-seq）和单核染色质可及性测序（snATAC-seq）对95名健康个体（年龄从2个月到88岁）的外周血单核细胞进行了分析，这些个体包括婴儿（n = 27）、儿童（n = 23）、成年人（n = 18）和老年人（n = 27）。黏膜相关恒定T细胞（MAIT）和γδ T细胞呈现出“先升后降”的模式，即在儿童期上升，在青年期达到峰值，随后随年龄增长而下降。CD8 T细胞受衰老影响最大，幼稚T细胞减少，颗粒酶K（GzK）阳性CD8 T细胞和终末分化记忆效应T细胞（TEMRA细胞）增加。婴儿的髓系/淋巴细胞比例较低，其组成具有独特性，表现为CD16单核细胞和浆细胞样树突状细胞的频率增加，而CD14单核细胞和传统树突状细胞的频率降低。他们的适应性免疫区室也表现出独特特征，包括T细胞和B细胞中组成性的干扰素刺激基因表达，以及幼稚CD4、幼稚CD8和γδ T细胞中SOX4阳性群体的扩增，该群体占幼稚T细胞池的约30%。SOX4阳性幼稚CD4 T细胞表现出Th2表观遗传特征。这一图谱为人类免疫系统在整个生命周期中的动态变化提供了关键见解，突出了婴儿免疫系统的独特特征。
