The surface barrier system, including both mucosa and skin, is continuously exposed to infinite beneficial and harmful antigens including commensal and pathogenic microbe, in handling its day-to-day duties. The digestive tract is thus equipped with the mucosal immune system (MIS) offering the first line of surveillance and defense forces against invasion of undesired antigens and pathogens. At same time, the MIS also creates a homeostatic condition to an enormous number and volume of innocuous and/or instructive antigens (e.g. commensal microorganisms and foods) which need to be appropriately "ignored". Mounting an immunologically harmonized response therefore represents a key decision-making process of active and/or quiescent immune responses by the MIS. To this end, the MIS has been shown to be enriched with the variety of innate and acquired immunity-associated cells. Our studies have provided a new evidence for the intra-tissue habitation of commensal flora (e.g. Alcaligenes) in the organized lymphoid structure associated with gut mucosa (e.g. Peyer’s patch:PP) which involves in the development of IgA immune system and creation of homeostatic condition. Recent evidences have suggested that intestinal innate lymphoid cells (ILCs) play a critical role in the containment of Alcaligenes in PP. Intestinal epithelial cells(ECs) possess unique α(1,2)- fucose- moiety and these cells are thus referred as fucosylated ECs (F-ECs) which are contributing in the formation of co-habitation platform for commensal bacteria. These F-ECs are induced and regulated by mucosal ILCs. The other group of innate immunity-associated cells, mast cells (MCs) expressing P2X7 purinoceptors play critical role in the induction and regulation of intestinal inflammation via extracellular ATP. In contrast, skin MCs do not express P2X7. Their distinct expression of P2X7 on mucosal and skin MCs is regulated by their surrounding environments. Thus, our data provide a new perspective of the surface connections with innate immunity associated cells, epithelial cells and microbiota for the mucosal and skin mutualisums and the disruption of the trialogue surface barrier connection system may lead to the development of pathological condition including undesired inflammation and allergy.