The transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner

Abstract

Asthma is a chronic inflammatory airway disease characterized by airway hyperreactivity, increased mucus production, and reversible airway contraction. Asthma is a complex genetic trait caused by environmental factors in genetically predisposed individuals. The transportation of maternal antigen-specific IgG via amniotic fluid, placenta and breast milk plays an important role in passive immunity. First, to examine whether maternal passive immunity by the transportation of antigen-specific IgG via FcRn regulates allergic airway inflammation, ovalbumin-immunized FcRn+/− female mice were bred with FcRn−/− male mice to evaluate the degree of ovalbumin-induced allergic airway inflammation of FcRn−/− offspring. Maternal passive immunity regulated allergic airway inflammation in an FcRn-dependent manner. Second, to examine the role of maternal antigen-specific IgG1 injection into mothers, we intravenously injected ovalbumin-specific IgG1 into wild-type or FcRn+/− mice immediately after they gave birth. The offspring were sensitized and challenged with ovalbumin. Antigen-specific IgG1 administered to lactating mice reduced allergic airway inflammation in their offspring in an FcRn-dependent manner. Last, to exclude the factor of maternal passive immunity other than ovalbumin-specific IgG1, we administered ovalbumin-specific IgG1 orally to offspring after birth. Oral administration of ovalbu-min-specific IgG1 to offspring during the lactating period prevented the development of allergic airway inflammation in an FcRn-dependent manner. These data show that the transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner.

A comprehensive review of the neonatal Fc receptor and its application in drug delivery

“…The expected presence of FcRn in the mammary tissue was firstly demonstrated in lactating mice (Cianga et al, 1999). IgG transport was confirmed in an asthma model supporting the role of FcRn in the transfer of passive immunity and tolerance induction (Nakata et al, 2010). FcRn is found to be widely distributed over malignant tissues, in ductal, lobular and medullary carcinoma, in histiocytes within the breast cancer interstitium, and in metastasizing epithelial cells within the lymph nodes (Cianga et al, 2003).…”

Antibodies and Their Receptors: Different Potential Roles in Mucosal Defense

“…In rodent models, FcRn also has a potentially important role in transmission of IgG from the breast milk of allergic mothers which has been shown to decrease the severity of allergic disease in the suckling offspring (87–89). This pathway is probably limited to species where materno-fetal transfer of IgG takes place through breastfeeding, and is thus not applicable to humans where IgG is almost exclusively transferred to the neonate before birth via the placenta.…”

Induction of Oral Tolerance in Neonatal Mice by Transfer of Food Allergens as IgA-Immune Complexes in Breast Milk

“…Involvement of this pathway has been noticed lately in the induction of oral tolerance by breastfeeding in neonates and prevention of asthma development [31] [32]. However, neither OVA nor OM IgG-IC was detected in our mouse milk samples (data not shown), probably due to the suppression of IgG synthesis in mother mice by the diet-induced oral tolerance.…”