Immune cell profiling reveals diverse niches of immune residents of the enteric nervous system and potential neuroimmune interactions.

Gastrointestinal (GI) neuroimmune interactions are crucial sensors and regulators of tissue homeostasis. Most enteric neurons reside within the myenteric plexus of the enteric nervous system in the muscular region, forming a structure called the muscularis externa. Despite established interactions between muscularis macrophages and neurons, the presence and function of other immune cell types remains poorly characterized. Here, we mapped the muscularis immune cell landscape, revealing that diverse cell types are present within distinct locations of the GI tract, and they lie in proximity to neuronal cell bodies and their axons. Using a hypothesis-free computational approach, we identify putative ligand-receptor interactions from publicly available single-cell RNA datasets and further validate one of these (App-CD74). This study provides a valuable reference to encourage new avenues of research underpinning enteric neuroimmune interactions as key contributors to GI homeostasis and diseases.