Regulation of immune tolerance to the intestinal microbiota

The host and the symbiotic microbiota within the intestine live in close association with each other. Setting up this symbiosis requires mutiple regulatory circuits from both the host and the microbiome side. Particularly, adaptive immunity including T cells need to be tolerized to prevent constant immune activation upon recognition of harmless microbes. We have identified one of the key cell types mediating this immune tolerance, namely the so-called ROR(γt)⁺ regulatory T cells. These cells are induced locally within the intestinal tract and are critical to induce oral tolerance and regulate inflammatory bowel disease as well as type 2 immune disorders, e.g. allergies. Both microbial factors and host pathways affecting the differentiation of ROR(γt)⁺ Tregs and therefore intestinal homeostasis will be discussed. Furthermore this concept opens the way for the identification of microbial 'dysbiosis' without the need to fully characterize complex microbial communities.