The crosstalk between enteric nervous system and immune system in intestinal development, homeostasis and diseases

The gut is the largest digestive and absorptive organ, which is essential for induction of mucosal and systemic immune responses, and maintenance of metabolic-immune homeostasis. The intestinal components contain the epithelium, stromal cells, immune cells, and enteric nervous system (ENS), as well as the outers, such as gut microbiota, metabolites, and nutrients. The dyshomeostasis of intestinal microenvironment induces abnormal intestinal development and functions, even colon diseases including dysplasia, inflammation and tumor. Several recent studies have identified that ENS plays a crucial role in maintaining the immune homeostasis of gastrointestinal (GI) microenvironment. The crosstalk between ENS and immune cells, mainly macrophages, T cells, and innate lymphoid cells (ILCs), has been found to exert important regulatory roles in intestinal tissue programming, homeostasis, function, and inflammation. In this review, we mainly summarize the critical roles of the interactions between ENS and immune cells in intestinal homeostasis during intestinal development and diseases progression, to provide theoretical bases and ideas for the exploration of immunotherapy for gastrointestinal diseases with the ENS as potential novel targets.