Implications of Paneth cell dysfunction on gastrointestinal health and disease

Abstract

Purpose of review: Paneth cells are specialized, secretory epithelial cells located in the small intestine. Although their existence was first described in 1872, their precise role in the gut remained unclear for over a century. Over the past few decades, elegant studies have shown Paneth cells play a key role enhancing gut barrier function, as niche cells for the intestinal stem cell compartment and via secreting antimicrobial peptides to establish an antimicrobial barrier at the epithelial surface. This review describes what is known about Paneth cell biology from human and animal studies with a focus on their putative role in clinical gastrointestinal disease.

Recent findings: Recent work has demonstrated important associations of dysfunctional Paneth cells with several gastrointestinal disorders. These include Crohn's disease, enteric infections, graft-versus-host disease, necrotizing enterocolitis, and environmental enteric dysfunction. Ongoing studies are examining precisely how Paneth cell biology is altered in these various disease states.

Summary: By understanding the mechanisms of Paneth cell regulation - and how these processes go awry in specific gastrointestinal diseases - we set the stage for using Paneth cells as biomarkers for disease progression and developing novel therapeutics that augment Paneth cell function to treat a spectrum of gastrointestinal disorders.

Fig 1.. Microscopic appearance of Paneth cells.

(A) Representative tissue section from mouse jejunum (H&E stain, 100x magnification). The Paneth cells are located at the base of the crypts, recognized by their highly distinct eosinophilic granules. (B) Electron micrograph of a mouse ileal crypt (2000x magnification). Paneth cells are characterized by their electron-dense, apically positioned cytoplasmic granules.

Fig 2.. Paneth cell-mediated regulation of intestinal barrier function.

(1) Paneth cells support proliferating stem cells by secreting epithelial growth factor (EGF), Wnt3, and Notch ligands. (2) Paneth cells also secrete antimicrobial peptides (AMPs) into the gut lumen that defend against enteric pathogens and regulate the composition of the enteric microbiota. Adapted from “Keystone Gut Microbiota Species Provide Colonization Resistance to Invading Bacteria” (2020), by Biorender.com. Retrieved from https://app.biorender.com/biorender-templates