Placental inflammation-driven T cell memory formation promotes allergic responses in offspring via endogenous glucocorticoids.

Abstract

Maternal exposure to environmental change during pregnancy is a critical determinant of offspring health and disease. Previous epidemiological studies have reported that maternal inflammation is linked to an increased incidence of postnatal allergy in offspring, although the underlying mechanisms remain largely unexplored. In this study, we employed a lipopolysaccharide-induced maternal inflammation murine model and found that offspring from dams with maternal immune activation (MIA) exhibited heightened allergic responses to house dust mite allergen. MIA offspring showed an increase in CD4⁺ T cell responses, which were mediated by increased T cell survival after activation, leading to promoting central and resident memory T cells formation. During maternal inflammation, TNF-α was identified as a crucial cytokine driving the heightened allergic response in offspring. TNF-α activates placental neutrophil, leading to placental necrosis. In parallel with placental damage, MIA offspring demonstrated increased glucocorticoid secretion in response to stress. Blockade of the glucocorticoid pathway during the sensitization phase mitigated the enhanced T cell memory response in MIA offspring, highlighting a mechanism by which maternal inflammation potentially modulates immune responses in offspring. Our findings elucidate one of the pathways by which maternal inflammation can influence postnatal immune regulation in offspring.