Weeratunga Praveen, Hunter Bethany, Sergeant Martin, Bull Joshua, Clelland Colin, Denney Laura, Vuppusetty Chaitanya, Burgoyne Rachel, Woo Jeongmin, Hu Tian, Borthwick Lee, Shaw James, Antanaviciute Agne, Filby Andrew, Byrne Helen, Fisher Andrew, Ho Ling-Pei
MRC Translational Immune Discovery Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nat Commun. 2025 Aug 4;16(1):7150. doi: 10.1038/s41467-025-61880-1.
Healthy alveolar repair relies on the ability of alveolar stem cells to differentiate into specialized epithelial cells for gas exchange. In chronic fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF), this regenerative process is abnormal but the underlying mechanisms remain unclear. Here, using human lung tissue that represents different stages of disease and a 33-plex single-cell imaging mass cytometry (IMC), we present a high-resolution, temporo-spatial cell atlas of the regenerating alveolar niche. With unbiased mathematical methods which quantify statistically enriched interactions, CD206macrophage subtype and an alveolar basal intermediate epithelial cell emerge as the most statistically robust spatial association in the epithelial and immune cell interactome, found across all stages of disease. Spatially resolved receptor-ligand analysis further offers an in silico mechanism by which these macrophages may influence epithelial regeneration. These findings provide a foundational step toward understanding immune-epithelial dynamics in aberrant alveolar regeneration in IPF.
健康的肺泡修复依赖于肺泡干细胞分化为专门的上皮细胞以进行气体交换的能力。在诸如特发性肺纤维化（IPF）等慢性纤维化肺部疾病中，这种再生过程是异常的，但其潜在机制仍不清楚。在这里，我们使用代表疾病不同阶段的人类肺组织和33重单细胞成像质谱流式细胞术（IMC），展示了再生肺泡生态位的高分辨率时空细胞图谱。通过量化统计上富集的相互作用的无偏数学方法，CD206巨噬细胞亚型和肺泡基底中间上皮细胞在所有疾病阶段的上皮和免疫细胞相互作用组中，作为统计学上最稳健的空间关联出现。空间分辨的受体-配体分析进一步提供了一种计算机模拟机制，通过该机制这些巨噬细胞可能影响上皮再生。这些发现为理解IPF中异常肺泡再生的免疫-上皮动力学迈出了基础的一步。
