Digestive tract is continuously exposed to infinite beneficial and harmful antigens including commensal and pathogenic microbe via the large mucosal epithelium. The intestinal mucosal surface is thus equipped with multi-complexed but harmonized biological components including epithelial-mesenchymal cells, mucosal immunocompetent cells and commensal microbiota, which form “Mucosal Multi-ecosystem” for the establishment of beneficial symbiosis condition as well as cooperative defense force. As an example, our study identified that commensal bacteria, Alcaligenes species can create “intra-tissue co-habitation niche” in Peyer’s patches (PPs), an example of commanding tissue for the induction and regulation of a balanced mucosal immunity. Innate lymphoid cells (ILCs) type3 have been shown to play critical role by the cooperative interaction with epithelial cells for the creation of intra-tissue co-habitation. Further, ILC3s have been shown to regulate epithelial cell glycosylation [e.g., fucosyltransferase 2 (Fut2) mediated fucosylation] for the creation of healthy gut microbiota and providing protective barrier against gut pathogens. The other form of innate immunity-associated cells, mast cells (MCs) expressing P2X7 purinoceptor are also involved in the maintenance or disruption of healthy gut environment via the extracellular ATP and P2X7 cascade.
Further, our most recent study has suggested that Paneth cells located in the crypt region of epithelium contain Fut2-dependent population (Fut2+Paneth cells). The development and function of Fut2+ Paneth cells are regulated by commensal bacteria dependent ILC3. These results suggested that the mucosal multi-ecosystem is a key element of creation and regulation of healthy environment of the intestinal tract for the balancing act between elimination and symbiosis.