Innate lymphoid cell (ILC) lineages mirror those of CD4+ T helper cell subsets, producing type 1, 2 and 3 cytokines respectively. Studies in adult human populations have shown contributions of non-cytotoxic ILC to immune regulation or pathogenesis in a wide range of diseases and have prompted investigations of potential functional redundancy between ILC and T helper cell compartments in neonates and children. To investigate the potential for ILC to contribute to immune responses across the human lifespan, we examined the numbers and frequencies of peripheral blood ILC subsets in a cohort of Gambians aged between 5 and 73 years of age. ILC2 were the most abundant peripheral blood ILC subset in this Gambian cohort, while ILC1 were the rarest at all ages. Moreover, the frequency of ILC1s (as a proportion of all lymphocytes) was remarkably stable over the life course whereas ILC3 cell frequencies and absolute numbers declined steadily across the life course and ILC2 frequencies and absolute numbers declined from childhood until the age of approx. 30 years of age. Age-related reductions in ILC2 cell numbers appeared to be partially offset by increasing numbers of total and GATA3+ central memory (CD45RA-CCR7+) CD4+ T cells, although there was also a gradual decline in numbers of total and GATA3+ effector memory (CD45RA-CCR7-) CD4+ T cells. Despite reduced overall abundance of ILC2 cells, we observed a coincident increase in the proportion of CD117+ ILC2, indicating potential for age-related adaptation of these cells in childhood and early adulthood. While both CD117+ and CD117- ILC2 cells produced IL-13, these responses occurred predominantly within CD117- cells. Furthermore, comparison of ILC frequencies between aged-matched Gambian and UK young adults (25–29 years) revealed an overall higher proportion of ILC1 and ILC2, but not ILC3 in Gambians. Thus, these data indicate ongoing age-related changes in ILC2 cells throughout life, which retain the capacity to differentiate into potent type 2 cytokine producing cells, consistent with an ongoing role in immune modulation.

先天淋巴细胞 (ILC) 谱系反映了 CD4+ T 辅助细胞亚群的谱系，分别产生 1、2 和 3 型细胞因子。对成人人群的研究表明，非细胞毒性 ILC 对多种疾病的免疫调节或发病机制的贡献，并促使对新生儿和儿童 ILC 和 T 辅助细胞区室之间潜在的功能冗余的研究。为了研究 ILC 在整个人类生命周期中促进免疫反应的潜力，我们检查了一组年龄在 5 至 73 岁之间的冈比亚人外周血 ILC 亚群的数量和频率。ILC2 是这个冈比亚队列中最丰富的外周血 ILC 亚群，而 ILC1 是所有年龄段中最稀有的。而且，ILC1 的频率（作为所有淋巴细胞的比例）在整个生命过程中非常稳定，而 ILC3 细胞频率和绝对数量在整个生命过程中稳步下降，ILC2 频率和绝对数量从儿童时期一直下降到大约 10 岁。30岁。ILC2 细胞数量与年龄相关的减少似乎被总和 GATA3+ 中央记忆 (CD45RA-CCR7+) CD4+ T 细胞数量的增加部分抵消，尽管总和 GATA3+ 效应记忆 (CD45RA-CCR7) 的数量也逐渐下降-) CD4+ T 细胞。尽管 ILC2 细胞的总体丰度降低，但我们观察到 CD117+ ILC2 的比例同时增加，表明这些细胞在儿童期和成年早期具有与年龄相关的适应潜力。CD117+ 和 CD117- ILC2 细胞都产生 IL-13，这些反应主要发生在 CD117 细胞内。此外，年龄匹配的冈比亚人和英国年轻人（25​​-29 岁）之间的 ILC 频率比较显示，冈比亚人的 ILC1 和 ILC2 比例总体较高，但 ILC3 比例不高。因此，这些数据表明 ILC2 细胞在整个生命过程中持续发生与年龄相关的变化，这些变化保留了分化为有效的 2 型细胞因子产生细胞的能力，这与免疫调节中的持续作用一致。