Advancements in neonatology over the past few decades have considerably increased the survival rate of premature newborns [1]. Bronchopulmonary dysplasia (BPD), one of the most common serious complications in preterm infants, affects >60 % of extremely preterm infants (gestational age < 28 weeks) [2,3]. As a multifactorial chronic lung disease, BPD is associated with various factors, including mechanical ventilation, oxygen toxicity, prenatal infection, and pulmonary inflammation [4,5]. The BPD phenotype has undergone a transformation—from a fibrocystic disease predominantly impacting late preterm infants to a disease characterized by impaired parenchymal development and dysregulated vascular growth, primarily affecting infants born before the gestational age of 29 weeks [6,7]. BPD can reduce premature infant survival substantially. It can also impair lung function during adulthood and potentially impact neurodevelopment in affected individuals [8,9]. The elucidation of mechanisms underlying BPD occurrence and identification of effective preventive and therapeutic strategies for BPD are essential for enhancing the current understanding of the condition.

Despite various immune cells potentially being involved in lung development, their precise contributions have not been elucidated completely [10,11]. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells released in response to biological stress, such as tissue damage and inflammation [12,13]. Based on their surface phenotypes and morphologies, MDSCs are typically divided into two major subtypes: polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs) [14]. MDSCs have fundamental roles in various biological processes and diseases, exhibiting both protective and pathogenic effects depending on the condition [15,16]. Inflammation-induced tissue damage contributes to the onset of numerous critical neonatal conditions within the initial weeks after birth, specifically BPD, necrotizing enterocolitis, and sepsis [17]. The observed expansion of MDSCs in healthy neonates indicates their potential role in broadly controlling inflammation. Moreover, MDSCs are currently considered an integral component of the intricate system protecting the fetus during gestation [18,19]. However, BPD-specific alterations and functions in MDSCs have not been reported thus far.

In the current study, we used animal cell culture, as well as molecular and immunological techniques, to identify the mechanisms underlying the role of MDSCs in BPD. Our findings may reveal novel targets that could be leveraged to develop therapeutic strategies.