Affect of maternal IgA on the developing small intestinal epithelium. Affect of maternal IgA on the developing small intestinal epithelium

Breast milk is associated with multiple benefits for the infant, including reduced incidence of chronic diseases such as Inflammatory Bowel Disease. We investigated the role of milk-derived maternal IgA (matIgA) on the developing small intestinal immune system. Using a model, where genotypically identical pups were fed by dams differed only in IgA production we revealed that matIgA regulates the assembly of the infant small intestinal microbiota and epithelium, supporting Lactobacillaceae and suppressing Enterobacteriaceae and the development of secretory lineage cells. Via the microbiota, MatIgA also regulated infant immune cells and suppressed early activation of Th17 cells. We demonstrated that Enterobacteriaceae-specific CD4+ T cells, activated in the absence of matIgA, persisted long term where they may contribute to subsequent inflammatory episodes. This work suggests that maternal IgA shapes the mucosal immune response by regulating the early-life microbiota thus preventing the development of inflammatory microbiota-specific T cells with memory potential. Overall design: small intestinal EpCAM + cells were sorted at 14, 24, and 42 day of life from IgA -/+ mice fed by either a C57BL/6 or Igha-/- dam.

母乳与婴儿的多项健康获益密切相关，可降低炎症性肠病（Inflammatory Bowel Disease）等慢性疾病的发病率。本研究探究了乳汁源性母体免疫球蛋白A（milk-derived maternal IgA，matIgA）对发育中小肠免疫系统的调控作用。我们采用仅在免疫球蛋白A（Immunoglobulin A，IgA）产生能力上存在差异的母鼠喂养基因型一致的幼崽的动物模型，结果显示matIgA可调控婴儿小肠菌群与上皮细胞的组装，促进乳杆菌科（Lactobacillaceae）的定植，同时抑制肠杆菌科（Enterobacteriaceae）的增殖以及分泌型谱系细胞的发育。借助肠道菌群，matIgA还可调控婴儿的免疫细胞，并抑制Th17细胞（T helper 17 cells）的早期活化。我们证实，在缺乏matIgA的条件下活化的肠杆菌科特异性CD4阳性T细胞（CD4+ T cells）会长期存留，此类细胞可能会在后续引发炎症事件。本研究表明，母体免疫球蛋白A通过调控生命早期的肠道菌群，塑造黏膜免疫应答，从而阻止具有记忆潜能的菌群特异性炎症性T细胞的发育。整体实验设计：从分别由C57BL/6母鼠或Igha-/-母鼠喂养的IgA +/-幼鼠中，于出生后14、24和42日分选小肠上皮细胞黏附分子阳性（Epithelial Cell Adhesion Molecule，EpCAM+）细胞。