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Background <p>Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity and long-term respiratory complications in preterm neonates. Effective strategies for moderate-severe BPD are currently lacking.</p> Methods <p>Tracheal aspirate (TA) samples were collected from 62 preterm neonates, and the immune cell composition was analyzed using multicolor flow cytometry. Subsequently, CD14<sup>+</sup> monocytes were isolated and purified from the TA samples for transcriptomic sequencing analysis. Cytokine arrays and enzyme-linked immunosorbent assays were utilized in the cytokine level detection from TA samples. Finally, we evaluated the efficacy of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor in alleviating lung inflammation resembling BPD in a neonatal rat model of hyperoxia lung injury.</p> Results <p>CD14<sup>+</sup>monocytes in TA samples from patients with BPD were significantly increased, and exhibited a pro-inflammatory transcriptomic profile, producing large amount of GM-CSF in the airway. Upregulated toll-like receptor 9 (TLR9) expression in these monocytes was observed. Baricitinib, a JAK1/JAK2 inhibitor, effectively reduced lung inflammation induced by hyperoxia and GM-CSF in a neonate rat model mimicking BPD.</p> Conclusions <p>GM-CSF derived from airway pro-inflammatory monocytes exacerbated inflammation in preterm neonates with BPD, particularly in moderate-severe cases. Baricitinib emerges as a promising therapeutic option, offering new hope for mitigating the inflammatory burden associated with moderate-severe BPD.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Moderate-to-severe bronchopulmonary dysplasia in preterm infants is closely linked to the sustained production of high levels of GM-CSF (granulocyte-macrophage colony-stimulating factor) by airway inflammatory monocytes. We propose a local GM-CSF–driven inflammatory positive-feedback loop in airway of patients with BPD. Interrupting the downstream GM-CSF signaling pathway may hold promise as the next effective therapeutic strategy.</p> </ItemContent> </UnorderedList></p>

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Proinflammatory monocyte-derived granulocyte-macrophage colony-stimulating factor fuels airway inflammation in bronchopulmonary dysplasia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月28日

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  • ShuShu Wang,
  • Xuesong Wang,
  • Dongyao Wang,
  • Binqing Fu,
  • Mingwu Chen,
  • Yong Lv,
  • Huiru Wang,
  • Haoquan Zhou,
  • Yonggang Zhou,
  • Haiming Wei

摘要

Background

Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity and long-term respiratory complications in preterm neonates. Effective strategies for moderate-severe BPD are currently lacking.

Methods

Tracheal aspirate (TA) samples were collected from 62 preterm neonates, and the immune cell composition was analyzed using multicolor flow cytometry. Subsequently, CD14+ monocytes were isolated and purified from the TA samples for transcriptomic sequencing analysis. Cytokine arrays and enzyme-linked immunosorbent assays were utilized in the cytokine level detection from TA samples. Finally, we evaluated the efficacy of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor in alleviating lung inflammation resembling BPD in a neonatal rat model of hyperoxia lung injury.

Results

CD14+monocytes in TA samples from patients with BPD were significantly increased, and exhibited a pro-inflammatory transcriptomic profile, producing large amount of GM-CSF in the airway. Upregulated toll-like receptor 9 (TLR9) expression in these monocytes was observed. Baricitinib, a JAK1/JAK2 inhibitor, effectively reduced lung inflammation induced by hyperoxia and GM-CSF in a neonate rat model mimicking BPD.

Conclusions

GM-CSF derived from airway pro-inflammatory monocytes exacerbated inflammation in preterm neonates with BPD, particularly in moderate-severe cases. Baricitinib emerges as a promising therapeutic option, offering new hope for mitigating the inflammatory burden associated with moderate-severe BPD.

Impact

Moderate-to-severe bronchopulmonary dysplasia in preterm infants is closely linked to the sustained production of high levels of GM-CSF (granulocyte-macrophage colony-stimulating factor) by airway inflammatory monocytes. We propose a local GM-CSF–driven inflammatory positive-feedback loop in airway of patients with BPD. Interrupting the downstream GM-CSF signaling pathway may hold promise as the next effective therapeutic strategy.