Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2017; 8(4): 150-160
Published online Nov 15, 2017. doi: 10.4291/wjgp.v8.i4.150
Paneth cells in intestinal physiology and pathophysiology
Nikolaus Gassler
Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, Braunschweig 38114, Germany
Author contributions: Gassler N contributed to the study idea, literature research, manuscript writing, and final revision.
Conflict-of-interest statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nikolaus Gassler, MA, Professor, Institute of Pathology, RWTH Aachen University, Celler Strasse 38, Braunschweig 38114, Germany. ngassler@ukaachen.de
Telephone: +49-531-5953310 Fax: +49-531-5953449
Received: January 24, 2017
Peer-review started: January 26, 2017
First decision: May 2, 2017
Revised: July 28, 2017
Accepted: August 15, 2017
Article in press: August 16, 2017
Published online: November 15, 2017
Processing time: 293 Days and 0.1 Hours
Abstract

Small intestinal mucosa is characterised by villus forming connective tissues with highly specialised surface lining epithelial cells essentially contributing to the establishment of the intestinal border. In order to perform these diverse functions, spatially distinct compartments of epithelial differentiation are found along the crypt-villus axis, including Paneth cells as a highly specialised cell type. Paneth cells locate in crypts and assist undifferentiated columnar cells, called crypt base columnar cells, and rapidly amplifying cells in the regeneration of absorptive and secretory cell types. There is some evidence that Paneth cells are involved in the configuration and function of the stem cell zone as well as intestinal morphogenesis and crypt fission. However, the flow of Paneth cells to crypt bottoms requires strong Wnt signalling guided by EphB3 and partially antagonised by Notch. In addition, mature Paneth cells are essential for the production and secretion of antimicrobial peptides including α-defensins/cryptdins. These antimicrobials are physiologically involved in shaping the composition of the microbiome. The autophagy related 16-like 1 (ATG16L1) is a genetic risk factor and is involved in the exocytosis pathway of Paneth cells as well as a linker molecule to PPAR signalling and lipid metabolism. There is evidence that injuries of Paneth cells are involved in the etiopathogenesis of different intestinal diseases. The review provides an overview of the key points of Paneth cell activities in intestinal physiology and pathophysiology.

Keywords: Antimicrobial peptide; Paneth cell; Crohn’s disease; Microbiome; Small intestine

Core tip: Paneth cells physiologically locate in small intestinal crypts. Wnt signalling promotes their differentiation and movement into crypts, whereas Notch activities antagonise Paneth cell maturation. The cells essentially contribute to crypt morphogenesis and intestinal homeostasis, sharpening the microbiome by secreting antimicrobial peptides, like defensins, and crypt fission. There is increasing molecular evidence that Paneth cells disorders are strongly involved in the pathophysiology of several intestinal diseases including ileal Crohn’s disease and necrotising enterocolitis.