A distinct experimental strategy to address this research question was recently reported by Nakata et al. Maternal transmission of allergen-specific IgG1 to breastfed FcRn-/- offspring was at levels 103-104 lower than observed in FcRn+/- or FcRn+/+ mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of RO4927350 allergen-specific IgE and associated pathology. Conclusions FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model. Background The beneficial effects of breastfeeding on infant health have been recognized for thousands of years across diverse civilizations [1]. As breast RO4927350 milk is the main source of passive immunity during the early months after birth, breastfeeding is considered to be the most effective means of preventing death in young children from infectious causes [2]. In addition, breastfeeding provides nutritional, developmental, psychological, social, economic, and environmental benefits [3]. While there is overwhelming evidence supporting the role of breastfeeding in protecting children from most immune-mediated diseases [4], the components in breast milk responsible for mediating this protection are not well defined. Maternal transfer of IgG endows offspring with short-term protective immunity [5-7]. The human fetus acquires a substantial amount of maternal IgG em in utero /em , transported across the placenta by the neonatal Fc receptor (FcRn) [8]. In both humans and rodents, maternal IgG is acquired from breast milk [9,10], absorbed from the gut lumen via FcRn-dependent transcytosis in intestinal epithelial cells [11-14]. It is known that mice deficient in either chain of FcRn (-chain or Rabbit polyclonal to PCDHB16 2 microglobulin) have impaired capacity to absorb maternal IgG from breast milk and accelerated decay of all IgGs, but not other Ig isotypes [13,15-19]. The structure of FcRn is well characterized [12,20] and several studies demonstrate a dynamic role of this receptor beyond the neonatal period [21,22]. It remains uncertain how maternal IgG acquired from breast milk impacts the susceptibility or severity of allergic diseases in children. It is known from animal models that offspring that receive serum fractions containing high titers of maternal antigen-specific IgG have suppressed IgE responses and enhanced IgG responses following immunization [23]. Similarly, the presence of maternal allergen-specific IgG1 at the time of immunization can inhibit IgE responses directed against the same allergen [24,25]. In contrast, passive transfer of allergen-specific IgG1 followed by local allergen challenge within the respiratory tract can induce airway eosinophilia accompanied by hyperresponsiveness to irritants (analogous to induced bronchoconstriction in RO4927350 asthmatics) [26]. The effect of passive immunization on exacerbation of allergic airway disease (AAD) appears mediated by enhanced allergen uptake in airway antigen presenting cells capable of activating proinflammatory CD4+ T cells [27]. We demonstrated that the breast milk from allergic mothers can protect offspring from ovalbumin (OVA)-induced AAD; with the protective effect dependent on intact maternal B cell immunity [28]. Offspring nursed by wildtype allergic foster mothers have less severe OVA-induced AAD than offspring nursed by B cell deficient allergic foster mothers. The.