Department of Pediatrics, Women and Children's Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children; Chongqing Research Center for Prevention & Control of Maternal and Child Diseases and Public Health, Chongqing, 401147, China.
Department of Neonatal Diagnosis and Treatment Center, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400015, China.
Sci Rep. 2024 Aug 29;14(1):20089. doi: 10.1038/s41598-024-70877-7.
Bronchopulmonary dysplasia (BPD) is the most common sequela of prematurity and is characterized by alveolar simplification and lung angiogenesis failure. The aim of this study was to explore the immune signatures of BPD. Differentially expressed gene analysis and immune infiltration analysis were conducted to identify key immune cell types and related genes by using the mRNA-seq dataset GSE25286. The expression patterns of key genes were validated in the scRNA-seq dataset GSE209664 and in experiments. The cell-cell crosstalk of key immune cells was explored with CellChat. We found that differentially expressed genes between BPD mice and controls were mostly enriched in leukocyte migration and M1 macrophages were highly enriched in BPD lungs. Hub genes (Cybb, Papss2, F7 and Fpr2) were validated at the single-cell level, among which the downregulation of Cybb was most closely related to macrophage infiltration. The reduced mRNA and protein levels of Cybb were further validated in animal experiments. Colocalization analysis of Cybb and macrophage markers demonstrated a significant decrease of Cybb in M1 macrophages. Cell-cell crosstalk found that alveolar epithelial cells interacted actively with macrophages through MIF-(CD74 + CD44) signalling. In conclusion, M1 macrophages played important roles in promoting BPD-like lung injury, which was correlated with a specific reduction of Cybb in macrophages and the potential activation of MIF signalling.
支气管肺发育不良（BPD）是早产儿最常见的后遗症，其特征是肺泡简化和肺血管生成失败。本研究旨在探讨 BPD 的免疫特征。通过使用 mRNA-seq 数据集 GSE25286 进行差异表达基因分析和免疫浸润分析，确定关键免疫细胞类型和相关基因。在 scRNA-seq 数据集 GSE209664 和实验中验证了关键基因的表达模式。使用 CellChat 探索关键免疫细胞的细胞-细胞串扰。我们发现 BPD 小鼠和对照组之间的差异表达基因主要富集在白细胞迁移中，M1 巨噬细胞在 BPD 肺中高度富集。在单细胞水平验证了枢纽基因（Cybb、Papss2、F7 和 Fpr2），其中 Cybb 的下调与巨噬细胞浸润最密切相关。动物实验进一步验证了 Cybb 的 mRNA 和蛋白水平降低。Cybb 和巨噬细胞标志物的共定位分析表明，M1 巨噬细胞中 Cybb 明显减少。细胞-细胞串扰发现肺泡上皮细胞通过 MIF-（CD74+CD44）信号与巨噬细胞积极相互作用。总之，M1 巨噬细胞在促进 BPD 样肺损伤中起重要作用，这与巨噬细胞中 Cybb 的特异性减少和 MIF 信号的潜在激活相关。
