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.
Highlights
The intestinal epithelium separates the diverse and ubiquitous members of the intestinal luminal microbiome, virome, and mycobiome from the largest population of resident immune cells anywhere in the body, forming our largest single barrier to the external environment [1,2,3,4]
Kuhn et al demonstrated that the early inhibition of IL-6 in murine models of bacterial colitis and wounding by biopsy impaired colon wound healing by limiting epithelial proliferation. They demonstrated by in situ hybridization that IL-6 mRNA transcripts were enriched within the mucosa surrounding sites of intestinal perforation in human patients, suggesting that this IL-6-driven mechanism of wound healing may be important in humans. These findings suggest that while Paneth cells may be crucial for IL-6-induced epithelial proliferation in the small intestine, other mechanisms exist for IL-6 to drive epithelial repair in the colon [45]
Cytokines and chemokines are critical for intestinal epithelial homeostasis and responses to disease
Summary
The intestinal epithelium separates the diverse and ubiquitous members of the intestinal luminal microbiome, virome, and mycobiome from the largest population of resident immune cells anywhere in the body, forming our largest single barrier to the external environment [1,2,3,4]. The majority of intestinal epithelial cells are absorptive enterocytes, but the epithelium contains a number of more specialized cell types, including Paneth cells (in the small intestine only), goblet cells, hormone-secreting enteroendocrine cells, microfold (M) cells, and tuft cells [2, 5]. Even these subtypes are too generalized to fully reflect the diversity
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