Mechanisms and risk factors for perinatal allergic disease

Abstract

Allergies are among the top causes of chronic disease in children. Their pathogenesis classically involves T helper 2 (Th2)-type inflammation driven by IgE-mediated allergen sensing. Triggers influencing allergic disease occur early in life, including before birth. The immature fetal immune system and mucosal barriers undergo periods of plasticity that are open to longitudinal programming by maternal influence. Evidence supports the importance of the maternal immune system in shaping perinatal immunity, as the transfer of cytokines, antibodies, and cells promotes offspring protection from pathogens. However, the same components may lead to allergic predisposition. Maternal-fetal interactions are further modified by epigenetic, metabolic, dietary, and microbiome-mediated effects. Here, we review how diverse maternal exposures and mediators signal across the placenta and through nursing perinatally to promote future tolerance or enhance reactivity against allergens. Improved understanding of the mechanisms predisposing for allergic disease in early life can guide the development of new therapeutics and preventative lifestyle modifications.