Single‐cell RNA sequencing of peripheral blood mononuclear cells from bronchopulmonary dysplasia

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BACKGROUND: Bronchopulmonary dysplasia (BPD) is a severe respiratory disease that primarily affects premature infants, characterized by persistent inflammation and abnormal immune activation. This study aimed to elucidate the immunological mechanisms underlying BPD by integrating single-cell RNA sequencing with T/B cell receptor profiling of peripheral blood mononuclear cells (PBMCs) from preterm infants with BPD, complemented by validation in a murine BPD model. METHODS: We profiled PBMCs from preterm infants diagnosed with BPD and healthy controls, identifying 22 distinct cell clusters corresponding to major immune cell types. RESULTS: Significant alterations were observed in myeloid and lymphoid subsets, with neutrophils undergoing metabolic reprogramming toward oxidative phosphorylation. T and B cell subsets exhibited phenotypic and functional changes, with B cells serving as crucial interaction hubs in cell communication networks. Progenitor cell analysis in BPD mouse models revealed specific alterations in hematopoietic stem cells. Analysis of cell-cell communication networks highlighted intricate intercellular interactions in BPD, emphasizing a pivotal role for the BTLA-TNFRSF14 signaling axis in disease pathogenesis. Additionally, pharmacological blockade of BTLA in mouse models alleviated disease severity, suggesting its potential therapeutic effects through modulation of the BTLA-TNFRSF14 pathway. CONCLUSION: These findings enhance the understanding of the BPD immune microenvironment and lay the foundation for developing targeted immunomodulatory therapies. HIGHLIGHTS: Single-cell sequencing revealed immune cell profiles in bronchopulmonary dysplasia (BPD). Neutrophils underwent metabolic changes, and B cells were key in immune communication. Targeting B and T lymphocyte attenuator (BTLA)-TNFRSF14 signalling reduced BPD severity in mouse models, suggesting a potential therapy.