Paneth Cell Function in Intestinal Inflammation

Paneth cells are highly specialised secretory epithelial cells located at the base of the crypts of Lieberkühn in the small intestine. They play a central role in innate mucosal defence by releasing a repertoire of antimicrobial peptides, including α-defensins, lysozyme and secretory phospholipase A2, that shape the composition of the gut microbiota. Beyond direct microbial killing, Paneth cells contribute to epithelial renewal through niche support of intestinal stem cells and modulate immune responses via secretion of cytokines and growth factors. Dysfunctional Paneth cell activity has been implicated in the pathogenesis of inflammatory bowel diseases, notably Crohn’s disease, where genetic variants affecting autophagy and endoplasmic reticulum stress pathways lead to impaired peptide secretion, altered microbiota composition (dysbiosis) and barrier breakdown. Environmental factors such as diet, microbial metabolites and psychosocial stress further influence Paneth cell function, linking systemic cues to local inflammation. Understanding the regulatory networks that govern Paneth cell biology offers potential avenues for therapeutic intervention aimed at restoring mucosal homeostasis and preventing chronic intestinal inflammation.

Research from Nature Portfolio

Recent studies have uncovered mechanisms by which bile acid-dependent transcription factors NR1H4, NR1H3 and VDR regulate the transcription of antimicrobial peptides in Paneth cells across distinct regions of the small intestine. Chromatin accessibility at key promoter and enhancer loci determines the capacity of these factors to shape regional heterogeneity in peptide expression. Perturbation of this axis impairs the development of a robust antimicrobial barrier and contributes to defective microbial defence observed in models of Crohn’s ileitis, emphasising the interplay between metabolic signalling and Paneth cell–mediated immunity.

Paneth Cell Function in Intestinal Inflammation publication trend

The graph below shows the total number of articles in paneth cell function in intestinal inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Paneth cell: A secretory epithelial cell at the base of the small intestinal crypt that releases antimicrobial peptides and growth factors.

Antimicrobial peptide: A small, cationic molecule produced by epithelial or immune cells to disrupt microbial membranes and regulate the gut microbiota.

Intestinal crypt: A tubular gland in the intestinal lining where stem cells and Paneth cells reside and contribute to epithelial renewal.

Dysbiosis: An imbalance in the composition or function of the gut microbial community associated with disease.

References

1. Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides. Nature Communications (2023).
2. Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis. Gut Microbes (2024).
3. Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides. Frontiers in Immunology (2021).
4. Intestinal autophagy links psychosocial stress with gut microbiota to promote inflammatory bowel disease. Cell Death & Disease (2019).