Sex-specific in utero reprogramming of lung immunity

Area of Science:

• Immunology
• Environmental Health
• Respiratory Medicine

Background:

• Sex differences in respiratory disease susceptibility are known, but their developmental origins and prenatal influences are unclear.
• Lung mucosal immunity requires balancing defense and inflammation for homeostasis.
• Prenatal environmental exposures can impact immune system development.

Purpose of the Study:

• To investigate if prenatal benzene exposure causes sex-specific reprogramming of lung mucosal immunity during fetal development.
• To characterize immune responses in fetal and postnatal lungs of mice exposed prenatally to benzene.
• To determine the long-term effects of prenatal benzene exposure on innate immune populations.

Main Methods:

• Used a controlled inhalation exposure model in pregnant C57BL/6 mice.
• Assessed immune responses in fetal and postnatal lungs under baseline and viral challenge conditions.
• Analyzed immune cell function, cytokine production, and gene expression (DREAM, A20).

Main Results:

• Female offspring showed enhanced type I interferon signaling, improved viral clearance, but also exaggerated inflammation.
• Male offspring exhibited increased proinflammatory cytokine production after lipopolysaccharide challenge.
• Benzene-exposed offspring had persistently primed alveolar macrophages, indicating durable innate immune alterations.

Conclusions:

• Lung mucosal immune development is inherently sex-dependent.
• Prenatal benzene exposure interacts with fetal sex to durably reprogram respiratory immunity.
• In utero environmental exposures are critical determinants of sex-specific immune trajectories and postnatal infection responses.