The role of maternal immune responses in tolerance induction is poorly understood. 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. Maternal OVA sensitization prevented food anaphylaxis, OVA-specific IgE production, and intestinal mast cell expansion in offspring. 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. Breastfeeding by OVA-sensitized mothers or maternal supplementation with IgG-IC was sufficient to induce neonatal tolerance. FcRn-dependent antigen presentation by CD11c⁺ dendritic cells (DCs) in offspring was required for oral tolerance. Human breast milk containing OVA-IgG-IC induced tolerance in humanized FcRn mice. 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.

孕产妇免疫应答在耐受性诱导中的作用了解甚少。为了研究母体变应原致敏度是否会影响后代对食物过敏的敏感性，我们用卵清蛋白（OVA）对雌性小鼠进行了表皮致敏，然后进行了表皮致敏，并对其后代进行了OVA口服攻击。孕产妇OVA致敏可防止食物过敏，OVA特异性IgE产生以及后代肠道肥大细胞扩增。这种保护作用是通过母乳中的新生儿可结晶片段受体（FcRn）依赖性的母体IgG和OVA免疫复合物（IgG-IC）的转移以及后代中过敏原特异性调节性T（T reg）细胞的诱导介导的。由OVA敏感的母亲进行母乳喂养或母体补充IgG-IC足以诱导新生儿耐受。子代需要⁺后代的树突状细胞（DC）才能获得口服耐受性。含有OVA-IgG-IC的人乳可诱导人源化FcRn小鼠的耐受。总的来说，我们证明母体IgG-IC与后代FcRn的相互作用对于诱导T reg细胞应答和控制新生儿的食物特异性耐受性至关重要。