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Secretory Sorcery: Paneth Cell Control of Intestinal Repair and Homeostasis - PubMed

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Secretory Sorcery: Paneth Cell Control of Intestinal Repair and Homeostasis

Paul Cray et al. Cell Mol Gastroenterol Hepatol. 2021.

Abstract

Paneth cells are professional secretory cells that classically play a role in the innate immune system by secreting antimicrobial factors into the lumen to control enteric bacteria. In this role, Paneth cells are able to sense cues from luminal bacteria and respond by changing production of these factors to protect the epithelial barrier. Paneth cells rely on autophagy to regulate their secretory capability and capacity. Disruption of this pathway through mutation of genes, such as Atg16L1, results in decreased Paneth cell function, dysregulated enteric microbiota, decreased barrier integrity, and increased risk of diseases such as Crohn's disease in humans. Upon differentiation Paneth cells migrate downward and intercalate among active intestinal stem cells at the base of small intestinal crypts. This localization puts them in a unique position to interact with active intestinal stem cells, and recent work shows that Paneth cells play a critical role in influencing the intestinal stem cell niche. This review discusses the numerous ways Paneth cells can influence intestinal stem cells and their niche. We also highlight the ways in which Paneth cells can alter cells and other organ systems.

Keywords: ER stress; Paneth cells; damage; intestine; reversion.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1
Figure 1

Paneth cells of small intestine are found at the crypt base, intercalated among the active intestinal stem cells. Their close proximity allows them to interact with active intestinal stem cells in numerous ways. Illustrated here are interactions associated with Notch signaling, Wnt signaling, and provision of Paneth cell-derived lactate for use by active intestinal stem cells for oxidative phosphorylation. NAD+, oxidized nicotinamide adenine dinucleotide.

Figure 2
Figure 2

Paneth cells secrete factors, including IL17A, and are impacted by others, such as IL22 or TNFα, which can travel through the blood stream and have local and systemic effects. Paneth cells are induced by TNFα to secrete IL17, which can lead to increased barrier permeability and injury to other organs including kidney and liver. IL22 receptor signaling in Paneth cells promotes their maturation. However, excess IL22 leads to increased expression of genes associated with ER stress. Overt loss of Paneth cells is associated with increased incidence of necrotizing enterocolitis, bacterial infections, and persistent inflammation.

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