Integrative transcriptomic and functional profiling reveals neutrophil-associated immune dysregulation in bronchopulmonary dysplasia

作者：Sen Li, Shunyu Xie, Haoying Huang, Haixia Chen, Meiling Zhou, Wenhao Zhou, Huayan Zhang, Xiaohui Wang · 发表于：Respiratory Research · 年份：2026 · DOI：10.1186/s12931-026-03860-7 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Immune Response and Inflammation、Neonatal Respiratory Health Research

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants. Although inflammation is broadly recognized as a key contributor to BPD, the precise roles and underlying mechanisms of immune cells in BPD pathogenesis remain incompletely understood. Moreover, the absence of reliable early diagnostic tools impedes the prediction of disease progression and the implementation of timely interventions. We first analyzed public blood transcriptomic data from preterm infants (<32 weeks gestational age) to explore immune alterations in BPD. Subsequently, we isolated neutrophils from infants at postnatal day 14 for transcriptomic and flow cytometric analyses. Longitudinal complete blood count (CBC) data were retrospectively collected at birth, and on days 2, 7, 14, 21, and 28, to validate these findings; machine learning models were subsequently developed to predict disease severity, with performance evaluated using the area under the receiver operating characteristic curve (AUC). Finally, single-cell transcriptome analysis was performed on public lung data from hyperoxia-exposed neonatal mice, followed by experimental validation. Blood transcriptomic profiling revealed increased neutrophils and downregulated T cell response pathways in BPD patients. Neutrophils from BPD infants exhibited enhanced inflammatory signaling and downregulated T-cell activation pathways compared to preterm controls. Flow cytometry confirmed an increased presence of polymorphonucl...