UCL Respiratory, Division of Medicine, University College London, London, UK.
Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Sci Immunol. 2023 Dec 15;8(90):eadf9988. doi: 10.1126/sciimmunol.adf9988.
Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.
人类肺部发育的研究集中在上皮细胞和间充质细胞类型和功能上，但对于发育中的肺部免疫细胞知之甚少，尽管气道是出生后粘膜免疫的主要部位。一个悬而未决的问题是，组织驻留免疫细胞是否在组织发育过程中发挥作用。在这里，我们使用 scRNA-seq、smFISH 和免疫组织化学对人类胚胎和胎儿肺部免疫细胞进行了分析。在胚胎阶段，我们观察到了先天免疫细胞的早期波，包括先天淋巴细胞、自然杀伤细胞、髓样细胞和谱系祖细胞。在小管阶段，我们检测到表达高水平细胞毒性基因的幼稚 T 淋巴细胞和成熟 B 淋巴细胞的存在，包括 B-1 细胞。我们的分析表明，胎儿肺部为 B 细胞完全成熟提供了一个小生境。鉴于发育过程中免疫细胞的存在和多样性，我们还研究了它们对上皮成熟的可能影响。我们发现，IL-1β 驱动上皮祖细胞退出自我更新并分化为体外的基底细胞。在体内，IL-1β 产生的髓样细胞存在于整个肺部和上皮尖端附近，这表明免疫细胞可能指导人类肺部上皮发育。
