The intestinal neuro-immune axis: crosstalk between neurons, immune cells, and microbes

The gastrointestinal tract is densely innervated by a complex network of neurons that coordinate critical physiological functions. Here, we summarize recent studies investigating the crosstalk between gut-innervating neurons, resident immune cells, and epithelial cells at homeostasis and during infection, food allergy, and inflammatory bowel disease. We introduce the neuroanatomy of the gastrointestinal tract, detailing gut-extrinsic neuron populations from the spinal cord and brain stem, and neurons of the intrinsic enteric nervous system. We highlight the roles these neurons play in regulating the functions of innate immune cells, adaptive immune cells, and intestinal epithelial cells. We discuss the consequences of such signaling for mucosal immunity. Finally, we discuss how the intestinal microbiota is integrated into the neuro-immune axis by tuning neuronal and immune interactions. Understanding the molecular events governing the intestinal neuro-immune signaling axes will enhance our knowledge of physiology and may provide novel therapeutic targets to treat inflammatory diseases.

Automated summary

The gastrointestinal tract is regulated by a dense network of interconnected neurons that coordinate important physiological functions. Studies have shown complex interactions between gut neurons, immune cells, and epithelial cells, highlighting their roles in immune regulation and intestinal function. Integration of intestinal microbiota into the neuro-immune axis through tuning neuronal and immune interactions may offer new therapeutic targets for inflammatory diseases.