An Update Review on the Paneth Cell as Key to Ileal Crohn's Disease

Abstract

The Paneth cells reside in the small intestine at the bottom of the crypts of Lieberkühn, intermingled with stem cells, and provide a niche for their neighbors by secreting growth and Wnt-factors as well as different antimicrobial peptides including defensins, lysozyme and others. The most abundant are the human Paneth cell α-defensin 5 and 6 that keep the crypt sterile and control the local microbiome. In ileal Crohn's disease various mechanisms including established genetic risk factors contribute to defects in the production and ordered secretion of these peptides. In addition, lifestyle risk factors for Crohn's disease like tobacco smoking also impact on Paneth cell function. Taken together, current evidence suggest that defective Paneth cells may play the key role in initiating inflammation in ileal, and maybe ileocecal, Crohn's disease by allowing bacterial attachment and invasion.

Mitochondrial Metabolism in the Intestinal Stem Cell Niche—Sensing and Signaling in Health and Disease

“…PC defects are frequent in CD and have been extensively investigated (Wehkamp and Stange, 2020). PCs directly sense the microbial environment and release their AMP-filled granules to shape the microbiota and prevent microbial invasion; thus, the observed dysfunctional PC morphology has been linked to IBD-associated dysbiotic changes of the microbiota, comprising decreased species richness and altered bacterial composition (Vaishnava et al, 2008;Eom et al, 2018).…”

Qualitative Nitrogen Malnutrition Damages Gut and Alters Microbiome in Adult Mice. A Preliminary Histopathological Study

“…In fact, normality was restored by returning to standard diet. Those findings are of interest, since current evidence suggests that defective Paneth cells may play a key role in promoting gut inflammation and also in Crohn’s disease, by allowing bacterial attachment and invasion [ 73 ].…”

Does an Apple a Day Also Keep the Microbes Away? The Interplay Between Diet, Microbiota, and Host Defense Peptides at the Intestinal Mucosal Barrier

“…However, in another cohort in Australia, reduced levels of HD5 were associated with inflammation and not with the NOD2 genetic status (45). Yet, despite that Paneth cells are the predominant cell types expressing NOD2 at the intestinal mucosa, it is unclear whether mutations in NOD2 are indeed causing the altered expression of the human defensins in ileal Crohn's disease (159).…”