Maternal-derived anti-commensal IgG promotes the induction of colonic peripheral regulatory T cells 3454

Description Immunoglobulin A (IgA) is the most abundant and widely studied antibody isotype in the intestines. However, maternal-derived IgG is readily detectable in the colon mucus of suckling mice including during the period when colonic IgA levels fall. However, the local functions of this IgG, particularly in promoting host-microbiota mutualism, are not fully understood. Preliminary data showed colonic Foxp3+RORγt+ peripheral Treg (pTreg) cell numbers decreased in IgG-deficient adult mice relative to wild-type mice. Colonic pTreg cells are believed to differentiate primarily during early life as microbial antigens are transferred into the lamina propria via goblet cell-associated antigen passages (GAPs). Thus, we hypothesized that maternal-derived IgG is important in early life colonic pTreg cells induction. Relative to pups receiving IgG-sufficient breast milk, pups that received breastmilk deficient in either total or T-dependent IgG harbored significantly reduced numbers of colonic pTreg cells, whether or not the pups were themselves capable of producing IgG. The effect of maternal IgG was dependent on the neonatal Fc receptor (FcRn), which is expressed by apical enterocytes but not goblet cells. Accordingly, inhibition of GAPs formation in IgG-deficient pups appeared to additively impair pTreg cells induction. Collectively, our study reveals a novel role for maternal-derived T-dependent IgG in promoting early life colonic immune tolerance development via induction of pTreg cells.