Figure 6.

A schematic illustration of the interactions between the gut immune and enteric nervous systems in the intestinal mucosa. Bidirectional communication between enteric nerves and immune cells regulates the local environment of the gut. Some of the cellular mediators of neuroimmune signaling in the gut are illustrated. There is extensive multidirectional signaling between intestinal epithelial cells (enterocytes, goblet cells, tuft cells, and enteroendocrine cells), enteric nerves, and enteric glia. Enteric nerves receive and integrate information from enteroendocrine cells, gut microbiota, and enteric glia; they also communicate with enteric glia, epithelia, the microbiota, and various populations of immune cells. Tuft cells and goblet cells are key mediators of epithelial-immune signaling, and tuft cells also signal to enteric nerves. Details of the specific molecular signaling mechanisms are described in the text. A cryptopatch is an aggregate of lymphoid cells found in the intestinal lamina propria. 5-HT, serotonin; ACh, acetylcholine; CGRP, calcitonin gene-related peptide; GFL, glial cell line-derived neurotrophic factor family ligand; IL, interleukin; ILC2, type 2 innate lymphoid cell; ILC3, type 3 innate lymphoid cell; NMU, neuromedin U; SP, substance P; VIP, vasoactive intestinal peptide. Image created with BioRender.com, with permission.