Neural control of goblet cells in the gastrointestinal tract

The mucus layer is an essential physical barrier that protects and lubricates mucosal surfaces in the body. The semipermeable nature of the mucus layer limits bacterial interactions with the epithelium while allowing nutrient absorption. Goblet cells (GCs) are specialized epithelial cells with a classical role to synthesize and secrete mucus to maintain the mucus layer. Emerging research has revealed the diverse nature of GC functions, including their interaction with the immune system through goblet cell-associated antigen passages to promote tolerance to dietary and bacterial antigens. Dysfunction of GCs or the mucus layer leaves the epithelium vulnerable to infection and is commonly associated with digestive disease. As such, there is a growing appreciation for the importance of GCs and the mucus layer to regulate mucosal homeostasis and protect against disease. Long-standing anatomical and pharmacological evidence indicates that the nervous system is a key regulator of GC function. However, the relative contribution from each division of the nervous system to the control of GC function is poorly defined. This is partly due to conflicting evidence from the literature and differences in experimental methods used. Furthermore, whether neurotransmitters influence GC functions and the associated mucus barrier directly or via indirect mechanisms, such as enhanced fluid secretion, remains unclear. The emergence of highly specific genetic approaches provides new opportunities to examine how specific nerve types can influence GC function. In this review, we consolidate the literature to date, with a focus on the stomach and lower gastrointestinal tract, and outline how current technologies may be useful to progress our fundamental understanding of neural-GC control.