Paneth cells and their multiple functions

Abstract

The small intestine mucosa is lined by specialized cells that form the crypt-villus axis, which expands its surface. Among the six intestinal epithelial cell types, the Paneth cell is located at the base of the crypt, and it contains numerous granules in its cytoplasm, composed of antimicrobial peptides, such as defensins and lysozyme, and growth factors, such as epidermal growth factor, transforming growth factor-α, and Wnt ligands. Together, these elements act in the defense against microorganisms, regulation of intestinal microbiota, maintenance, and regulation of stem cell identity.Pathologies that target Paneth cells can disturb such defense activity, but they also affect the maintenance of the stem cell niche. In that way, Crohn's disease, necrotizing enterocolitis, and graft-versus-host disease promote a reduction of Paneth cell population, and, consequently, secretion of their products into the lumen of the crypts, making the affected organism predisposed to infections and dysbiosis. Additionally, the emergence of new intestinal cells is also decreased. This review aims to address the main characteristics of Paneth cells, highlighting their multiple functions and the importance of their preservation to ensure bowel homeostasis.

Loss of Paneth cells dysregulates gut ILC subsets and enhances weight gain response to high fat diet in a mouse model

“…Beside their role in the secretion of anti-microbial products, Paneth cells regulate the gut immune homeostasis through secretion of cytokines including IL-17A and TNF-α [22–25]. Our analysis of immune cell subsets in the small intestines of wild-type and Sox9 ΔIEC mice showed striking differences in their ILC populations.…”

“…It has been shown that Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface through production of anti-microbials and cytokines [20,21]. Thus, Paneth cells produce a-defensins, lysozyme, and phospholipase A2, and contribute to immune homeostasis through production of cytokines (TNF-a and IL-17A) [22][23][24][25]. As a main source of anti-microbial products in the gut, Paneth cells are believed to play a protective role in the development of metabolic disorders and obesity [20,[26][27][28].…”

Breastfeeding lifespan control of growth, maintenance, and metabolism of small intestinal epithelium

“…Besides the molecules involved, Paneth cells are the epithelial component of stem cell niche (Beumer & Clevers, 2021) and for maintenance of the intestinal microbiota, and they integrate a highly organized physical and immunological barrier (Barreto E Barreto et al, 2022). Molecular mechanisms leading to changes in secretory Paneth cells have been linked to inflammatory bowel diseases, such as Crohn's disease and necrotizing enterocolitis (Barreto E Barreto et al, 2022). It is evident that the dedifferentiation of Paneth cells is dependent on the constitutive activation of Notch pathway in the intestinal epithelium (Yu et al, 2018), and on its target Hes1.…”

“…In the stomach, previous studies reported that EW increases the proliferation and anticipates the maturation of mucous neck and zymogenic cells in the gastric mucosa of rat pups (Ghizoni et al, 2014; Zulian et al, 2017), and part of these effects extend to adulthood (Teles Silva et al, 2020). The intestinal niche in the crypt depends on signaling and on the organization with Paneth cells (Barreto E Barreto et al, 2022). Among the targets of the Wnt pathway, Ascl2 expression is essential for Lgr5+ stem cell maintenance, and its loss is associated with crypt hyperplasia and pouch‐like projections on the villi (van der Flier et al, 2009).…”

“…In the stem cell compartment, we observed that EW increased the number of Paneth cells/crypt at 18 and 60 pnd when compared to S group (p < 0.05), and at 120 pnd both S and EW rats showed higher rates than the 18 pnd counterparts (Figure 2a,b). As Paneth cells secrete defensins (Barreto E Barreto et al, 2022), we also evaluated Defa24 (defensin) mRNA expression and registered an increase at 18 pnd after EW (p < 0.05) (Figure 2c).…”