The role of enteric glia in intestinal immunity

Abstract

The nervous system and immune system are important interfaces of the gastrointestinal tract that sense, integrate and respond to environmental stimuli and challenges. Enteric glial cells (EGCs), the non-neuronal cells of the enteric nervous system, were long considered mere bystanders only providing support for their workhorse neuronal neighbours. However, work by many groups has demonstrated that EGCs are important nodes in the intestinal tissue circuitry that regulate gastrointestinal barrier function, immunity, host defence and tissue repair. More recent studies have also begun to uncover the cellular interactions and molecular mechanisms that underpin the important functions of EGCs in intestinal physiology and pathophysiology. Here, we review recent literature investigating the roles of EGCs in intestinal immunity and tissue homeostasis.

Figure 1

Functional units of enteric glia and other cell types in the gut control immune homeostasis and the response to infectious and inflammatory challenge. Depicted on the left are the homeostatic roles of enteric glial cells (light blue) in maintaining the intestinal epithelium and the inflammatory tone of the tunica muscularis. In response to pathogen invasion (e.g. helminth parasites), inflammation or tissue injury (e.g. irradiation), enteric glial cells are activated (red) and produce a range of diffusible factors or express cell-surface molecules to control immune responses and tissue repair. CCL2: chemokine (C-C motif) ligand 2, LPS: Lipopolysaccharide, Cxcl10: C-X-C motif chemokine ligand 10, M-CSF: macrophage colony-stimulating factor, MHCII: major histocompatibility complex class II, IFNγ: interferon gamma, GDNF: glia-derived neurotrophic factor. Figure created with BioRender.com.