ILC2 influence the differentiation of alveolar type II epithelial cells in bronchopulmonary dysplasia mice.

Bronchopulmonary dysplasia, a common complication of premature infants, is mainly characterized by blocked alveolarization. Proverbially, the injury of alveolar type II epithelial cells is regarded as the pathologic basis of occurrence and development of bronchopulmonary dysplasia. In the case of alveolar epithelial damage, alveolar type II epithelial cells can also differentiate to alveolar type I epithelial cells as progenitor cells. During bronchopulmonary dysplasia, the differentiation of alveolar type II epithelial cells becomes abnormal. Group 2 innate lymphoid cells can produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Previous studies have shown that group 2 innate lymphoid cells can inhibit the alveolarization process of bronchopulmonary dysplasia by secreting IL-13. However, whether group 2 innate lymphoid cells can affect the differentiation of alveolar type II epithelial cells in the pathologic process of bronchopulmonary dysplasia remains unclear. In this study, we have shown that IL-13 secreted by group 2 innate lymphoid cells increased during bronchopulmonary dysplasia, which was related to the release of large amounts of IL-33 by impaired alveolar type II epithelial cells. This led to abnormal differentiation of alveolar type II epithelial cells, reduced differentiation to alveolar type I epithelial cells, and increased transdifferentiation to mesenchymal cells through the epithelial-mesenchymal transition. Taken together, our study provides a complementary understanding of the development of bronchopulmonary dysplasia and highlights a novel immune mechanism in the pathogenesis of bronchopulmonary dysplasia.

Type 2 innate lymphoid cell-derived amphiregulin regulates type II alveolar epithelial cell transdifferentiation in a mouse model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants characterized by alveolar growth arrest. Interleukin (IL)-33 and type 2 innate lymphoid cell (ILC2) affect type II alveolar epithelial cell (AECII) differentiation in BPD mice and may cause increased lung epithelial-mesenchymal transition (EMT). Amphiregulin (AREG) can be produced by ILC2 and is associated with tissue repair. However, the action mechanism of AREG produced by ILC2 to alveolar development in BPD is unclear. In this study, we aimed to demonstrate the role and mechanism of AREG in influencing AECII transdifferentiation in the lung tissue of BPD mice. The effects of ILC2-derived AREG on AECII transdifferentiation were verified in vivo and in vitro, and the role of IL-33 on ILC2-derived AREG in AECII transdifferentiation in BPD mice and a preliminary investigation of the role of AREG's receptor-epidermal growth factor receptor (EGFR) on AECII transdifferentiation. The results showed that neonatal mice developed severe lung injury after hyperoxia, and IL-33 induced AREG production via ILC2 affected normal AECII differentiation and promoted EMT. In addition, the blockade of EGFR was found to alleviate the impaired AECII differentiation under hyperoxia in an in vitro study. In summary, our study demonstrates that AREG secreted by ILC2 affects AECII transdifferentiation in BPD mice, which provides a new idea for the clinical treatment of BPD.

IL-33-ST2 pathway regulates AECII transdifferentiation by targeting alveolar macrophage in a bronchopulmonary dysplasia mouse model.

Evidence points to the indispensable function of alveolar macrophages (AMs) in normal lung development and tissue homeostasis. However, the importance of AMs in bronchopulmonary dysplasia (BPD) has not been elucidated. Here, we identified a significant role of abnormal AM proliferation and polarization in alveolar dysplasia during BPD, which is closely related to the activation of the IL-33-ST2 pathway. Compared with the control BPD group, AMs depletion partially abolished the epithelialmesenchymal transition process of AECII and alleviated pulmonary differentiation arrest. In addition, IL-33 or ST2 knockdown has protective effects against lung injury after hyperoxia, which is associated with reduced AM polarization and proliferation. The protective effect disappeared following reconstitution of AMs in injured IL-33 knockdown mice, and the differentiation of lung epithelium was blocked again. In conclusion, the IL-33-ST2 pathway regulates AECII transdifferentiation by targeting AMs proliferation and polarization in BPD, which shows a novel strategy for manipulating the IL-33-ST2-AMs axis for the diagnosis and intervention of BPD.

[Structural features of intestinal flora in preterm rats with cognitive impairment: an analysis based on high-thorough sequencing].

OBJECTIVE: To study the structural features of intestinal flora in preterm rats with cognitive impairment and the association of the change in intestinal flora with cognitive impairment in preterm rats. METHODS: Sprague-Dawley rats at 16-17 days of gestation were intraperitoneally injected with lipopolysaccharide for two consecutive days to establish a model of cognitive impairment, and the rats treated with intraperitoneally injected phosphate-buffered saline were established as the control group. Cesarean section was performed on day 21 of gestation, and preterm rats were randomly assigned to healthy maternal rats for feeding. The place navigation test in the Morris water maze was used to evaluate cognition on day 30 after birth. According to the result, the preterm rats were divided into cognitive impairment group with 21 rats and normal control group with 10 rats. Hematoxylin and eosin staining was used to observe pathological changes of the hippocampus, and fecal samples were collected for 16S rRNA sequencing and analysis. A principal component analysis (PCA) was performed for intestinal flora. RESULTS: Compared with the normal control group, the cognitive impairment group showed degeneration and necrosis of a large number of neurons in the hippocampus. Compared with the normal control group, the cognitive impairment group had significant reductions in the abundance and diversity of intestinal flora (P<0.05), with a significant increase in the abundance of Proteobacteria at the phylum level (P<0.05), as well as significant reductions in the abundance of Prevotella and Lactobacillus and significant increases in the abundance of Staphylococcaceae and Oligella at the order, family, and genus levels (P<0.05). PCA showed a significant difference in the composition of intestinal flora between the two groups. CONCLUSIONS: There is a significant change in the structure of intestinal flora in preterm rats with cognitive impairment, which provides a basis for the treatment and intervention of microecological changes due to cognitive impairment after preterm birth.