Neutrophil extracellular traps promote bronchopulmonary dysplasia-like injury in neonatal mice via the WNT/ß-catenin pathway.

Background: Bronchopulmonary dysplasia (BPD) is one of the most common and severe chronic diseases in preterm infants. Premature infants are susceptible to BPD due to immature lungs and adverse perinatal episodes of infection, hyperoxia, and mechanical ventilation. Methods: Neutrophils are the first line of host defence, and the release of neutrophil extracellular traps (NETs) is an important strategy to immobilize and kill invading microorganisms. This study examined whether NETs were associated with BPD in preterm infants and contributed to hyperoxia-induced lung injury in neonatal mice via the WNT/ß-catenin pathway. Results: In this study, we found that preterm infants with BPD had higher levels of NETs in their tracheal aspirates than those without BPD. Neonatal mice treated with NETs after birth exhibited BPD-like changes in their lungs. Furthermore, the levels of Aquaporin 5 (AQP5) and surfactant-associated protein C (SPC), which represent alveolar differentiation and development, were significantly lower than those in the controls. The WNT/ß-catenin pathway is one of the most well-known signalling pathways involved in lung growth. We found that the expression of the target genes c-MYC, cyclin D, and vascular endothelial growth factor (VEGF) and the important proteins WNT3a and ß-catenin significantly decreased. Moreover, heparin, which is a NET inhibitor, attenuated changes in gene and protein expression, thereby attenuating BPD-like changes. Discussion: This finding indicates that NETs are associated with BPD and can induce BPD-like changes in neonatal mice via the WNT/ß-catenin pathway.

Th17/Treg imbalance is associated with reduced indoleamine 2,3 dioxygenase activity in childhood allergic asthma.

BACKGROUND: The differentiation of CD4+ lymphocytes Th17/regulatory T cells (Treg) and indoleamine 2,3-dioxygenase (IDO) is associated with the pathogenesis of allergic asthma. Basic research has shown that IDO is likely a "switch" of the transition from Th17 cells to Tregs under certain conditions. However, no relevant clinical studies have been reported on the association between IDO activity and Th17/Treg imbalance in children with allergic asthma. The goal of this study was to test whether indoleamine 2,3 dioxygenase (IDO) participates in the pathogenesis of pediatric allergic asthma by influencing Th17/regulatory T cell (Treg) differentiation and related cytokines. METHODS: Thirty-three children with allergic asthma and 33 healthy children were selected. The subjects were evaluated via a pulmonary function test, a skin prick test, and an eosinophil count. Peripheral blood was collected to measure Th17/Treg percentages and related cytokine levels. Blood and induced sputum were obtained to measure the IDO level. RESULTS: Compared with the control group, the patient group had an obvious Th17/Treg imbalance; their IDO levels were significantly lower, their IL-17 and IL-6 levels were markedly higher, and their IL-10 and TGF-ß levels were markedly lower than those of the control group. The IDO levels in both blood and induced sputum were negatively correlated with the Th17/Treg ratio. CONCLUSIONS: A significant correlation was observed between IDO activity and Th17/Treg imbalance in children with allergic asthma. IDO may upregulate Treg numbers by stimulating IL-10 production and inhibiting IL-6 expression. Therefore, IDO may be a molecular switch that leads to the conversion of Th17 cells to Tregs, thus playing a potentially protective role in the pathogenesis of asthma.Trial registration This study was approved by the Chinese Clinical Trial Registry with registration number ChiCTR-COC-15006080 and was reviewed and approved by the Ethics Committee of Southwest Hospital. The name of registration: The effect of indoleamine 2,3 dioxygenase (IDO) on Regulation of Th17/Treg Differentiation in Childhood Asthma. Date of registration: 14/03/2015. URL of trial registry record: http://www.chictr.org.cn.