Neonatal Mucosal Immune Stimulation by Microbial Superantigen Improves the Tolerogenic Capacity of CD103(+) Dendritic Cells

作者：Stern Anna; Wold Agnes E; Ostman Sofia^*

来源：PLos One, 2013, 8(9): e75594.

DOI：10.1371/journal.pone.0075594

Food allergy represents failure to develop tolerance to dietary proteins. Food allergy has increased in prevalence in parallel with decreased exposure to microbes during infancy. In mice, neonatal peroral exposure to the strongly T cell stimulating superantigen staphylococcal enterotoxin A (SEA), enhances the capacity to develop oral tolerance to a novel antigen encountered in adult life. A population of antigen-presenting cells in the gut, the CD103(+) dendritic cells (DCs), is thought to be involved in oral tolerance development, as they convert naive T cells into FoxP3(+) regulatory T cells (Treg). This function depends on their capacity to convert vitamin A to retinoic acid, carried out by the retinal aldehyde dehydrogenase (RALDH) enzyme. Here, newborn mice were treated with superantigen and DC function and tolerogenic capacity was examined at six weeks of age. We observed that, in mice fed superantigen neonatally, the CD11c(+) DCs had increased expression of RALDH and in vitro more efficiently induced expression Foxp3 expression to stimulated T cells. Further, these mice showed an accumulation of FoxP3(+) T cells in the small intestinal lamina propria and had a more Ag-specific FoxP3(+) T cells after oral tolerance induction in vivo. Moreover, the improved oral tolerance, as shown by increased protection from food allergy, was eradicated if the Vitamin A metabolism was inhibited. These observations contribute to the understanding of how a strong immune stimulation during the neonatal period influences the maturation of the immune system and suggests that such stimulation may reduce the risk of later allergy development.

• 出版日期2013-9-27