Inflammation during pregnancy primes the baby's immune system for allergies

It has long been known that inflammation in the mother during pregnancy increases the risk of allergic diseases in the child. New work in Mucosal Immunology shows the mechanism: inflammation in the placenta itself rewires the fetus's stress response and prolongs the survival/memory of T cells, which makes postnatal allergic reactions stronger.

Research methods

The team (KAIST) modeled maternal inflammation in mice by injecting lipopolysaccharide (LPS) during pregnancy. The authors then: (1) tested whether placental inflammation/damage occurs and what mediators are involved; (2) assessed how this affects the offspring axial stress response (glucocorticoids); (3) examined the survival and differentiation of memory T cells in the offspring; (4) performed allergen challenges (house dust mite) and assessed airway inflammation.

Key Results

• LPS induction in pregnant mice caused placental inflammation, increased TNF-α, neutrophil activation, and placental tissue damage.
• These changes modulated the stress axis in the offspring, increasing the secretion of endogenous glucocorticoids.
• Against this background, the offspring's T cells survived longer, more actively formed central/tissue memory, and gave an enhanced response upon repeated contact with the allergen.
• Exposure to dust mite allergen resulted in marked eosinophilic infiltration and airway hyperreactivity, a profile consistent with asthma.
• The article was published under the title: “Placental inflammation-driven T cell memory formation promotes allergic responses in offspring via endogenous glucocorticoids” (DOI: 10.1016/j.mucimm.2025.06.006).

Interpretation and clinical conclusions

The work suggests a clear chain: maternal inflammation → placental TNF-α/neutrophils → placental injury → remodeling of the glucocorticoid response in the fetus → enhanced T-cell memory → hyperergic allergy after birth. In practice, this highlights the importance of preventing and controlling inflammatory conditions during pregnancy, as well as the potential of placental inflammation biomarkers for early prediction of childhood asthma and allergy risk. (Human data needed: current results are preclinical, in mice.)

Authors' comments

• Significance of the work and practical conclusion.
  “ This will become an important scientific basis for the development of early prognostic biomarkers and the creation of prevention strategies for childhood allergic diseases,” notes Prof. Heung-Gyu Lee (KAIST).

• On the novelty of the mechanism (author's abstract from the abstract):
  " Our results clarify one of the pathways through which maternal inflammation can influence postnatal immune regulation in the offspring."

• The key link is the glucocorticoid pathway (from the abstract).
  " Blocking the glucocorticoid pathway during the sensitization phase attenuated the enhanced T-cell memory response in offspring with maternal immune activation."

• How the authors summarize the gist of the article in a public release.
  “ Our new study shows that placental inflammation, by forming T-cell memory, enhances allergic responses in the offspring via endogenous glucocorticoids,” wrote Prof. Heung-Gyu Lee.

• Context and “world first” (author’s position in press release):
  “ [This is] the first study in the world to show how the mother’s inflammatory response during pregnancy influences the fetal allergic immune system via the placenta.”

The authors say this is the first study to show how maternal inflammation “rewires” the fetal allergic immune system via the placenta, with endogenous glucocorticoids increasing T-cell survival and memory, which enhances postnatal allergic responses. They see this as a basis for developing early detection biomarkers and prevention strategies for childhood allergic diseases (such as asthma).