Both naturally occurring thymic-derived T reg cells and inducible T reg cells derived from conventional CD4 + T cells in the presence of TGF-β and specialized dendritic cells (DCs) such as CD11c +CD103 + DCs suppress Th2 responses ( Chatila, 2005 van Wijk et al., 2007 Curotto de Lafaille et al., 2008 Gri et al., 2008 Akdis and Akdis, 2011). However, whether maternal factors modulate T reg cell–mediated tolerance in offspring remains elusive. Nevertheless, whether active tolerance is induced in offspring has not been reported in these studies.įorkhead box protein 3 (Foxp3) + regulatory T (T reg) cells regulate Th2 responses and food allergy in humans and in mice ( Chatila, 2005 van Wijk et al., 2007 Littman and Rudensky, 2010 Ohkura et al., 2013 Noval Rivas et al., 2015). In contrast, maternal exposure and/or sensitization to food allergens could be beneficial for protection of offspring from allergic diseases in humans and in mice ( Fusaro et al., 2007 López-Expósito et al., 2009 Mosconi et al., 2010 Verhasselt, 2010b Bunyavanich et al., 2014 Frazier et al., 2014). Past studies have identified an increased risk ( Sicherer et al., 2010) or no association ( Lack et al., 2003) of maternal peanut consumption with peanut sensitization in offspring.
For example, effects of maternal allergen exposure on development of allergies in offspring have been controversial. However, how maternal factors influence food allergy in offspring remains largely unknown. Allergic reactions to foods often occur on the first known ingestion ( Sicherer et al., 1998), suggesting that exposure of offspring to food allergens may occur in utero and/or through breast milk. The disease is associated with CD4 + T cells that secrete Th2 cytokines, and allergen-specific IgE antibodies that activate mast cells ( Metcalfe et al., 2009). population, has no effective cure, and can be associated with life-threatening anaphylaxis ( Sicherer and Sampson, 2014). Collectively, we demonstrate that interactions of maternal IgG-IC and offspring FcRn are critical for induction of T reg cell responses and control of food-specific tolerance in neonates.įood allergy is a growing public health concern as it affects 5–8% of the U.S.
Human breast milk containing OVA-IgG-IC induced tolerance in humanized FcRn mice. FcRn-dependent antigen presentation by CD11c + dendritic cells (DCs) in offspring was required for oral tolerance. Breastfeeding by OVA-sensitized mothers or maternal supplementation with IgG-IC was sufficient to induce neonatal tolerance. This protection was mediated by neonatal crystallizable fragment receptor (FcRn)–dependent transfer of maternal IgG and OVA immune complexes (IgG-IC) via breast milk and induction of allergen-specific regulatory T (T reg) cells in offspring.
Maternal OVA sensitization prevented food anaphylaxis, OVA-specific IgE production, and intestinal mast cell expansion in offspring. To study whether maternal allergen sensitization affects offspring susceptibility to food allergy, we epicutaneously sensitized female mice with ovalbumin (OVA) followed by epicutaneous sensitization and oral challenge of their offspring with OVA. The role of maternal immune responses in tolerance induction is poorly understood.