Foxp3⁺ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis

Foxp3⁺ Tcells play a critical role for the maintenance of immune tolerance. Here we show that in mice, Foxp3⁺ Tcells contributed to diversification of gut microbiota, particularly of species belonging to Firmicutes. The control of indigenous bacteria by Foxp3⁺ Tcells involved regulatory functions both outside and inside germinal centers (GCs), consisting of suppression of inflammation and regulation of immunoglobulin A (IgA) selection in Peyer's patches, respectively. Diversified and selected IgAs contributed to maintenance of diversified and balanced microbiota, which in turn facilitated the expansion of Foxp3⁺ Tcells, induction of GCs, andIgA responses in the gut through a symbiotic regulatory loop. Thus,the adaptive immune system, through cellular and molecular components that arerequired for immune tolerance and through the diversification as well as selection of antibody repertoire, mediates host-microbial symbiosis by controlling the richness and balance of bacterial communities required for homeostasis.