Cytokine Tuning of Intestinal Epithelial Function

Abstract

The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

“…Nevertheless, we did note differential expression of other immune components in neonates (compared to adults), particularly IL-10 and IFN-Ɣ. IL-10 is a prototypical anti-inflammatory cytokine which inhibits the synthesis of pro-inflammatory cytokines such as TNF-ɑ and IFN-Ɣ thus limiting pathological cell shedding responses [23]. IL-10 induction has previously been described to be driven by certain microbiota members such as Bacteroides, Bifidobacterium and Helicobacter, suggesting that specific members may play a key role for inducing anti-inflammatory and anti-apoptotic responses, thereby driving protective barrier integrity during the neonatal period [24][25][26][27].…”

Astragalus polysaccharides alleviates LPS‐induced inflammation via the NF‐κB/MAPK signaling pathway

“…Cytokines and chemokines are essential for the gut immune response and disease. Cytokines directly promote or limit IEC proliferation, apoptosis, and permeability, thereby destroying the intestinal epithelial barrier (Andrews, Mclean, & Durum, 2018). Chemokines are responsible for chemotactic cell migration and play important roles in the humoral and cellular immune responses, inducing the production of corresponding inflammatory factors (Griffith, Sokol, & Luster, 2014; Hughes & Rjb, 2018; Zimmerman, Vongsa, Wendt, & Dwinell, 2010).…”

“…All images were taken in the center of the well. APS, Astragalus polysaccharides; LPS, lipopolysaccharide intestinal epithelial barrier (Andrews, Mclean, & Durum, 2018).…”

Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity

“…Among the immunomodulatory molecules that are produced by IECs, thymic stromal lymphopoietin, transforming growth factor (TGF)‐ β , retinoic acid and IL‐10 have been shown to impact a broad range of immune cells and have each earned their own detailed reviews . In addition to these well‐described modulators of immune cell function, IEC production of IL‐15 has recently been shown to be required for the homing of protective T‐cell receptor‐ γδ ‐positive (TCR‐ γδ + ) intraepiethlial lymphocytes (IELs) to the epithelium of the small intestine .…”

“…Among the immunomodulatory molecules that are produced by IECs, thymic stromal lymphopoietin, transforming growth factor (TGF)-b, retinoic acid and IL-10 have been shown to impact a broad range of immune cells and have each earned their own detailed reviews. [65][66][67][68] In addition to these well-described modulators of immune cell function, IEC production of IL-15 has recently been shown to be required for the homing of protective T-cell receptorcd-positive (TCR-cd + ) intraepiethlial lymphocytes (IELs) to the epithelium of the small intestine. 69 The TCR-cd + IEL surveillance behaviour, antimicrobial responses and protection against pathogens such as Salmonella Typhimurium and Toxoplasma gondii are dependent on MyD88 signalling in IECs; 70,71 however, the mechanisms of IEC-IEL communication required for these functions are still unknown.…”