Multifaceted involvements of Paneth cells in various diseases within intestine and systemically

Abstract

Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal bacterial translocation in necrotizing enterocolitis, liver disease, acute pancreatitis and graft-vs-host disease. Risk genes in PCs render intestine susceptible to Crohn’s disease. In intestinal infection, different pathogens induce varied responses in PCs, and toll-like receptor ligands on bacterial surface trigger the degranulation of PCs. The increased level of bile acid dramatically impairs PCs in obesity. PCs can inhibit virus entry and promote intestinal regeneration to alleviate COVID-19. On the contrary, abundant IL-17A in PCs aggravates multi-organ injury in ischemia/reperfusion. The pro-angiogenic effect of PCs aggravates the severity of portal hypertension. Therapeutic strategies targeting PCs mainly include PC protection, PC-derived inflammatory cytokine elimination, and substituting AMP treatment. In this review, we discuss the influence and importance of Paneth cells in both intestinal and extraintestinal diseases as reported so far, as well as the potential therapeutic strategies targeting PCs.

Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury

“…Paneth cells play a pivotal role in maintaining intestinal homeostasis, and their dysfunction is implicated not only in intestinal disorders but also in extraintestinal pathologies ( Cui et al., 2023 ). Paneth cells exert regulatory control over the abundance of mucosa-associated bacteria, thereby preventing direct contact with the epithelium and subsequent translocation of bacterial species ( Wallaeys et al., 2023 ).…”

Long Non-Coding RNAs and Their “Discrete” Contribution to IBD and Johne’s Disease—What Stands out in the Current Picture? A Comprehensive Review

“…An important genetic contributor is the NOD2/CARD15 gene, which is expressed apart from P cells in dendritic cells, macrophages, and intestinal epithelial cells (Figure 2); its risk variants are associated with lower levels of α-defensins in P cells, leading to impaired antimicrobial function. Importantly, autophagy gene ATG16L1 risk variants compromise the autophagy function of P cells in patients with CD [222], which is the most well-studied target as a risk gene for CD in P cells so far [223]. P cells serve a dual function (1) by supporting the surrounding LGR5 positive stem cells via Wnt signals and (2) through their antibacterial secretion, while P cells seems to be the main source of IL17, also leading to TNF production, which is constitutively expressed in the P cells of the crypts [150].…”

“…P cells serve a dual function (1) by supporting the surrounding LGR5 positive stem cells via Wnt signals and (2) through their antibacterial secretion, while P cells seems to be the main source of IL17, also leading to TNF production, which is constitutively expressed in the P cells of the crypts [150]. Importantly, P cells have been used as a major therapeutic target in the intestine [223].…”

Paneth cells in farm animals: current status and future direction

“…Paneth cells have been confirmed to be the guardians of small intestine in humans and mice [ 25 ]. However, less attention has been paid to Paneth cells in small intestine of farm animals.…”