Yu Boshi, Hong Guixuan, Li Yubai, Yan Xudong, Yu Zhangbin
Department of Neonatology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, 1017 North Dongmen Road, Shenzhen, Guangdong 518020, China.
Department of Neonatology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, 1017 North Dongmen Road, Shenzhen, Guangdong 518020, China.
Cell Immunol. 2025 Aug;414:104995. doi: 10.1016/j.cellimm.2025.104995. Epub 2025 Jun 14.
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.
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.
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.
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.
支气管肺发育不良（BPD）主要影响早产儿，其特征为肺发育受损、肺泡化减少和慢性炎症，可导致长期呼吸并发症。然而，BPD的临床预防治疗仍然具有挑战性。由于免疫细胞可能在BPD的发病机制和预防中发挥作用，我们研究了多形核骨髓来源的抑制细胞（PMN-MDSCs）在新生小鼠模型中是否能预防高氧诱导的BPD。
新生C57BL/6小鼠自出生起暴露于常氧（21%氧气）或高氧（85%氧气）环境。在出生后第3、7和14天，使用组织学技术[苏木精和伊红（H&E）染色及放射状肺泡计数（RAC）测量]分析肺发育情况。此外，我们使用流式细胞术鉴定肺骨髓来源的抑制细胞（MDSC）亚群。通过过继转移实验评估PMN-MDSCs在关键发育阶段的治疗潜力。通过组织学分析、肺泡和血管标志物的免疫荧光染色以及促炎细胞因子测量来评估肺组织中PMN-MDSC移植的结果。
与常氧对照组相比，暴露于高氧的小鼠表现出明显的肺损伤，包括肺泡增大且不规则、RAC降低以及体重减轻。高氧减少了PMN-MDSC数量，但增加了单核细胞MDSC数量。PMN-MDSC移植保留了肺泡结构，增加了肺泡和肺血管数量。免疫荧光染色证实肺泡和血管发育增强。最后，PMN-MDSCs降低了肺组织中的促炎细胞因子水平。
PMN-MDSCs可能通过促进新生小鼠的肺泡和血管发育以及减轻炎症来预防高氧诱导的肺损伤。有必要进一步研究阐明PMN-MDSCs保护作用的精确机制及其临床转化潜力。
