Mini-Review: Enteric glial regulation of the gastrointestinal epithelium

Abstract

Many enteric glia are located along nerve fibers in the gut mucosa where they form close associations with the epithelium lining the gastrointestinal tract. The gut epithelium is essential for absorbing nutrients, regulating fluid flux, forming a physical barrier to prevent the entry of pathogens and toxins into the host, and participating in immune responses. Disruptions to this epithelium are linked to numerous diseases, highlighting its central importance in maintaining health. Accumulating evidence indicates that glia regulate gut epithelial homeostasis. Observations from glial-epithelial co-cultures in vitro and mouse genetic models in vivo suggest that enteric glia influence several important features of the gut epithelium including barrier integrity, ion transport, and capacity for self-renewal. Here we review the evidence for enteric glial regulation of the intestinal epithelium, with a focus on these three features of its biology.

Figure 1.. Enteric glia are found in close proximity to the intestinal epithelium.

(A) Immunohistochemical staining of a small intestinal cross-section from a Vil1^CreRosa26^tdTomato/+Plp1^eGFP transgenic mouse in which enteric glia are labeled with green fluorescent protein (GFP) and intestinal epithelial cells are labeled with tdTomato. Mucosal glia closely associate with epithelial cells in villi (B) and in crypts (C). Scale bar = 20μm

Figure 2.. Enteric glia and other cells in the human colonic mesenchyme express machinery for barrier-modulating factors.

UMAP plots of gene expression (from adults with or without ulcerative colitis) [29]. Plp1 marks glia, Akr1c3 – Aldo-Keto Reductase Family 1 Member C3 (generates 11β-PGF2α).