Neonatal hyperoxia promotes asthma-like features through IL-33-dependent ILC2 responses

Area of Science:

• Pulmonary medicine
• Immunology
• Neonatal research

Background:

• Premature infants often require oxygen, leading to oxidative stress.
• Oxygen exposure increases the risk of chronic lung disease and asthma in preterm infants.

Purpose of the Study:

• To investigate the mechanisms linking neonatal hyperoxia to asthma development.
• To identify key cellular and molecular pathways involved in hyperoxia-induced asthma.

Main Methods:

• Mice exposed to neonatal hyperoxia and/or house dust mite antigen.
• Assessed airway hyperresponsiveness, inflammation, mucus production, and immune cell responses.
• Measured serum IL-33 and cytokine levels in infants and mice.

Main Results:

• Neonatal hyperoxia caused asthma-like features in mice, including airway inflammation and hyperresponsiveness.
• Elevated IL-33 and ILC2 responses were observed, driven by oxidative stress.
• IL-33 receptor signaling and ILC2s were essential for developing these asthma-like features.

Conclusions:

• An IL-33 and ILC2 axis is critical for neonatal hyperoxia-induced asthma.
• Targeting IL-33, ILC2s, and oxidative stress may prevent or treat asthma in preterm infants.