Polymorphonuclear myeloid-derived suppressor cells protect against hyperoxia-induced bronchopulmonary dysplasia in neonatal mice through suppression of excessive inflammatory response.

BACKGROUND

Bronchopulmonary dysplasia (BPD), which primarily affects premature infants, is characterized by impaired lung development, reduced alveolarization, and chronic inflammation, leading to long-term respiratory complications. However, clinical prevention treatment of BPD remains challenging. Because immune cells may have a role in BPD pathogenesis and prevention, we investigated whether polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) protect against hyperoxia-induced BPD in a neonatal mouse model.

METHODS

Neonatal C57BL/6 mice were exposed to either normoxia (21 % oxygen) or hyperoxia (85 % oxygen) since birth. Lung development was analyzed on postnatal days 3, 7, and 14 by using histological techniques [hematoxylin and eosin (H&E) staining and radial alveolar count (RAC) measurement]. Moreover, we used flow cytometry to identify lung myeloid-derived suppressor cell (MDSC) subsets. PMN-MDSCs' therapeutic potential at key developmental stages was evaluated through adoptive transfer experiments. PMN-MDSC transplantation outcomes in the lung tissues were assessed through histological analysis, immunofluorescence staining for alveolar and vascular markers, and proinflammatory cytokine measurement.

RESULTS

Hyperoxia-exposed mice exhibited considerable lung damage, including enlarged and irregular alveoli, low RACs, and decreased body weights compared with normoxic controls. Hyperoxia reduced PMN-MDSC numbers but increased monocytic MDSC numbers. PMN-MDSC transplantation preserved alveolar structure and increased alveolar and pulmonary vessel numbers. Immunofluorescence staining confirmed enhanced alveolar and vascular development. Finally, PMN-MDSCs reduced proinflammatory cytokine levels in lung tissues.

CONCLUSION

PMN-MDSCs may protect against hyperoxia-induced lung injury by promoting alveolar and vascular development and reducing inflammation in neonatal mice. Further research elucidating precise mechanisms underlying the protective effects of PMN-MDSCs and their potential for clinical translation is warranted.