Immune-epithelial crosstalk at the intestinal surface

Abstract

The intestinal tract is one of the most complex organs of the human body. It has to exercise various functions including food and water absorption, as well as barrier and immune regulation. These functions affect not only the gut itself, but influence the overall health of the organism. Diseases involving the gastrointestinal tract such as inflammatory bowel disease and colorectal cancer therefore severely affect the patient's quality of life and can become life-threatening. Intestinal epithelial cells (IECs) play an important role in intestinal inflammation, infection, and cancer development. IECs not only constitute the first barrier in the gut against the lumen, they also constantly signal information about the gut lumen to immune cells, thereby influencing their behaviour. In contrast, by producing various antimicrobial peptides, IECs shape the microbial community within the gut. IECs also respond to cytokines and other mediators of immune cells in the lamina propria. Interactions between epithelial cells and immune cells in the intestine are responsible for gut homeostasis, and modulations of this crosstalk have been reported in studies of gut diseases. This review discusses the wide field of immune-epithelial interactions and shows the importance of immune-epithelial crosstalk in the intestine to gut homeostasis and the overall health status.

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…Recent approaches focus on mechanistic modeling of the transport and disposition kinetics of chemical compounds in multilayered skin at the cellular level (Dancik et al, 2013;Kasting et al, 2013; secretion of mucins that form an additional protective barrier), Paneth cells (secretion of antimicrobial peptides) and entero-endocrine cells (secretion of hormones regulating motility and release of digestive enzymes). Other important cell types present are involved in antigen processing and mucosal immunity, for example intraepithelial lymphocytes and microfold (M) cells, which transport organisms and particles from the gut lumen across the epithelial barrier to immune cells (Kucharzik et al, 2000;Wittkopf et al, 2014).…”

Cathelicidin-BF suppresses intestinal inflammation by inhibiting the nuclear factor-κB signaling pathway and enhancing the phagocytosis of immune cells via STAT-1 in weanling piglets

“…Given that IL-10 inhibits IFN-induced genes by suppressing the tyrosine phosphorylation of STAT-1 [26,33], we investigated the expression of STAT-1 and p-STAT-1 in vivo and in vitro. Interestingly, we found that C-BF increased the phosphorylation of STAT-1 in the jejunum of weanling piglets compared to the control treatment.…”

“…IL-10 is a potent immunosuppressive molecule that mediates the down-regulation of Th1 responses by inhibiting the production of proinflammatory cytokines. The crucial role of IL-10 in the intestine was established based on the finding that IL-10-deficient mice spontaneously developed enterocolitis [26,[30][31][32]. In addition, IL-10 inhibits NF-κB activation in human monocytes [33].…”

“…These data suggest that C-BF treatment may reduce whole-body inflammation during the weaning period. The intestine is a complex biological system and is considered to be the largest immunological organ in mammals because it harbors 80% of all immune cells in the body [26]. Considering that intestinal immunity plays a crucial role in the inflammatory process during weaning, we examined the expression of inflammation-related and signaling pathway genes in the intestine.…”

Intestinal Metrnl released into the gut lumen acts as a local regulator for gut antimicrobial peptides

“…Intestinal epithelial cells are uniquely located at the border of luminal commensal microbiota and the lamina propria of the intestine [30,31] . Secretory intestinal epithelial cells can secrete mucins and antimicrobial proteins to establish a physical and biochemical barrier between the bacterial and epithelial surfaces [22,30] .…”