China
Africa
Explore chapters and articles related to this topic
The Paneth Cell and Its Role in the Development of NEC
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Brian A. Juber, Steven J. McElroy
Paneth cells are highly specialized epithelial cells located in the crypts of Lieberkühn and are most prevalent in the small intestine. They function to maintain a state of homeostasis in the small intestine, maintaining a normal microbial/host axis, and attenuating excess inflammation. While Paneth cells develop early in human gestation, they do not become immune competent until closer to term gestation, leaving preterm infants deficient in normal Paneth cell biology during the greatest window of susceptibility to develop NEC. Infants who have developed NEC have decreased Paneth cell numbers compared to age-matched controls, and ablation of murine Paneth cells results in a NEC-like phenotype. Thus, the current evidence supports a role for Paneth cells in the pathophysiology of NEC, and further study of this important cell type is warranted.
Secreted effectors of the innate mucosal barrier
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Michael A. McGuckin, Andre J. Ouellette, Gary D. Wu
Normally, Paneth cells are anatomically restricted to the small intestine. During conditions of inflammation, as in Barrett's esophagus, H. pylori gastritis, Crohn's disease, and ulcerative colitis, Paneth cells may appear ectopically. The “intermediate” or “granulo-goblet” cells (see Figure 4.4) are rare in healthy gut mucosa but may appear during episodes of inflammation. Reflecting the common progenitor of goblet cell and Paneth cell lineages, these cells produce mucins and contain small electron-dense cytoplasmic inclusions that are positive for Paneth cell-specific markers. Thus, pro-inflammatory conditions of diverse origin may induce the appearance of numerous intermediate cells that produce secretory proteins characteristic of both lineages.
Gastrointestinal Tract
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Judit E. Markovits, Graham R. Betton, Donald N. McMartin, Theresa Boulineau
Paneth cells, as part of the innate immune system, function to protect stem cells in small intestinal crypts that provide defense against ingested pathogens and control both the number and composition of commensal bacteria (Bevins 2004). Additionally, based on mouse studies, the interaction of Paneth cells and bacteria is needed for appropriate angiogenesis in villi for the development of adult-type villi, which become well vascularized during weaning. Paneth cells carry out these important functions in host defense by the secretion of lysozyme, zinc, and antimicrobial molecules (defensins). The unfolding protein response gene and autophagy have key roles in Paneth cell function. X-Box binding protein 1 (XBP1) influences antimicrobial activity and Paneth cell number and decreases responses to proinflammatory stimuli. Furthermore, mice with XBP1 deletion develop enteritis (Garrett et al. 2010). Several human diseases have been identified with underlying abnormal Paneth cell function, including Crohn’s disease, necrotizing enterocolitis of newborns, and cystic fibrosis (Bevins 2004).
Loss-of-function SLC30A2 mutants are associated with gut dysbiosis and alterations in intestinal gene expression in preterm infants
Published in Gut Microbes, 2022
Shannon L Kelleher, Samina Alam, Olivia C Rivera, Shiran Barber-Zucker, Raz Zarivach, Takumi Wagatsuma, Taiho Kambe, David I Soybel, Justin Wright, Regina Lamendella
Paneth cells (PCs) are considered the “gatekeepers of health”, and PC defects have been implicated in intestinal dysbiosis and numerous gastrointestinal disorders including dysmotility, colon cancer, inflammatory bowel disease (IBD), and necrotizing enterocolitis (NEC) in preterm infants.1Paneth cells are highly specialized secretory cells in the crypts of Lieberkühn that release large granules containing a variety of antimicrobial proteins, enzymes, cytokines, and growth factors that regulate the intestinal stem cell niche, manage the intestinal microbiome, modulate mucosal inflammation, and facilitate host microbial defense. Paneth cell granules also contain a remarkably high amount of zinc. Several lines of evidence suggest granule zinc depletion is pathogenic: severe zinc deficiency in humans causes PC granule zinc depletion and dysfunction,2 which can be remediated by zinc supplementation.2,3 Disruption of cellular zinc homeostasis using the zinc-specific chelator dithizone depletes granule zinc,4–6 which selectively kills PCs6 and leads to mucosal inflammation and intestinal permeability7 in rodent models. Moreover, dithizone administration followed by Klebsiella infection is commonly used as a preclinical mouse model of NEC,8 implicating PC granule zinc depletion in the pathogenesis of this disease. Thus, the ability to accumulate zinc in PC granules is critical for managing the composition of the gut microbiome and maintaining gastrointestinal health.
Gut microbiota: sculptors of the intestinal stem cell niche in health and inflammatory bowel disease
Published in Gut Microbes, 2021
Manasvini Markandey, Aditya Bajaj, Nicholas Edward Ilott, Saurabh Kedia, Simon Travis, Fiona Powrie, Vineet Ahuja
Paneth cells are localized to the base of the crypts and lie adjacent to the intestinal epithelial stem cells. They can sense microbial cues via TLR-Myd88 mediated pathways, in turn mounting antimicrobial defense by releasing anti-microbial peptides, lysozyme, and phospholipase A. However, it is now known that another way in which microbial sensing by Paneth cells can protect epithelial homeostasis is by the release of Wnt ligands and stem cell growth factors. Lactic acid, produced by gut bacteria such as Lactobacillus and Bifidobacterium sp., is sensed by G-protein-coupled receptors on Paneth cells, triggering the release of Wnt3 in the crypt environment. The consequent ISC proliferation and epithelial regeneration protects mice exposed to radiation- and chemotherapy-induced intestinal damage.68 Incidentally, lactic acid producing bacteria are well known as probiotic therapeutics for alleviating symptoms of IBD.69 Considering the role of lactic acid in maintenance of epithelial proliferation, the beneficial role of these probiotics in IBD, might be attributed to their ability to stimulate Wnt release from Paneth cells. In colonic crypts, the absence of Paneth-derived proliferative signals may be compensated by Wnt-producing Paneth cell-like populations, found to be inter-digitated between ISCs.70,71
Imbalance of the intestinal virome and altered viral-bacterial interactions caused by a conditional deletion of the vitamin D receptor
Published in Gut Microbes, 2021
Jilei Zhang, Yongguo Zhang, Yinglin Xia, Jun Sun
Paneth cells play an integral role in shaping the microbiome and host defenses. The absence of VDR in Paneth cells impairs antimicrobial function, affects microbial assemblage, and increases susceptibility to colitis and infection.37,71 The altered virome in VDRΔPC mice further indicated the important role of VDR and Paneth cells in shaping the intestinal microbiome and secreting antimicrobial peptides or metabolites. Paneth cells may indirectly impact the intestinal microbiota or the outcome of a viral infection by adjusting the population of bacteria. Paneth cells also play a key role in host defense by sensing microorganisms through TLRs.72 It is clear from our data that VDR deficiency in Paneth cell could lead to viral dysbiosis, which may further result in a compromised epithelial barrier.72