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Research Article: CCR1 + monocytes facilitating bronchopulmonary dysplasia through regulation of S100A8 and MMP8

Date Published: 2026-05-01

Abstract:
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and is characterized by aberrant late-stage lung development driven by multiple factors. Although previous studies have demonstrated that BPD is associated with prenatal and postnatal inflammatory stimuli, the inflammatory mechanisms involved immune cell populations have not been fully elucidated. Here, we systematically investigated the roles of myeloid cells in the inflammatory processes underlying BPD. Using single-cell transcriptomic data of normal and BPD mouse lung, we found that the proportions of several myeloid subpopulations were specifically upregulated in BPD lung, including CCR1 + monocytes, CD74 + macrophages, IL7R + macrophages, MARCO + macrophages, CD63 + neutrophils, and CD73 + neutrophils. However, we only validated the increased proportions of CCR1 + monocytes in human BPD blood through flow cytometry analysis. Combined with bulk transcriptome and detection in serum of human BPD blood, we identified S100A8 and MMP8 as highly expressed downstream factors of CCR1 + monocytes. Immunofluorescence staining further confirmed the presence of CCR1 + monocytes expressing S100A8 or MMP8 in the mouse BPD lung tissues and demonstrated their association with disease development. Finally, in CCR1 + monocytes isolated from the peripheral blood of BPD infants, we found that the NF-?B and AKT pathways regulate the production of S100A8 and MMP8 respectively. Our study explored the role and mechanism of CCR1 + monocytes associated with BPD, which offers valuable insights for the development of novel clinical biomarkers and therapeutic strategies for BPD.

Introduction:
Bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants, and its incidence has shown an increasing trend in recent years ( 1 ). BPD can occur at different stages of lung development and is caused by multifactorial injurious stimuli, including genetic and environmental factors. Histopathologically, BPD is characterized by arrested development, remodeling, and functional impairment of the airways, alveoli, mesenchyme, and pulmonary vasculature ( 2 , 3 ). BPD is not merely a pulmonary…

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