Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

Abstract

The intestinal tract is lined by a single layer of columnar epithelial cells that forms a dynamic, permeable barrier allowing for selective absorption of nutrients, while restricting access to pathogens and food-borne antigens. Precise regulation of epithelial barrier function is therefore required for maintaining mucosal homeostasis and depends, in part, on barrier-forming elements within the epithelium and a balance between pro- and anti-inflammatory factors in the mucosa. Pathologic states, such as inflammatory bowel disease, are associated with a leaky epithelial barrier, resulting in excessive exposure to microbial antigens, recruitment of leukocytes, release of soluble mediators, and ultimately mucosal damage. An inflammatory microenvironment affects epithelial barrier properties and mucosal homeostasis by altering the structure and function of epithelial intercellular junctions through direct and indirect mechanisms. We review our current understanding of complex interactions between the intestinal epithelium and immune cells, with a focus on pathologic mucosal inflammation and mechanisms of epithelial repair. We discuss leukocyte–epithelial interactions, as well as inflammatory mediators that affect the epithelial barrier and mucosal repair. Increased knowledge of communication networks between the epithelium and immune system will lead to tissue-specific strategies for treating pathologic intestinal inflammation.

Role of the intestinal mucosa in acute gastrointestinal GVHD

“…5 The mucosa itself is further subdivided into 3 layers. The epithelium is a single-cell layer lining the interior lumen of the gastrointestinal tract.…”

HuR Enhances Early Restitution of the Intestinal Epithelium by Increasing Cdc42 Translation

“…After damage to the epithelium, the intestinal mucosa exhibits a spectrum of responses and repairs itself quickly to restore epithelial integrity (1). In stressful environments, successful repair of wounds and ulcers requires epithelial cells to rapidly change gene expression patterns to regulate cell survival, migration, proliferation, and differentiation (2,3). Early epithelial restitution is a primary repair modality in the gastrointestinal tract, and it rapidly reseals superficial wounds by migrating visible remaining epithelial cells from areas adjacent to the injured surface to cover the wounded area, followed by proliferation and differentiation (4,5).…”

“…Early epithelial restitution is a primary repair modality in the gastrointestinal tract, and it rapidly reseals superficial wounds by migrating visible remaining epithelial cells from areas adjacent to the injured surface to cover the wounded area, followed by proliferation and differentiation (4,5). This early rapid mucosal reepithelialization after mucosal injury is a complex process that includes the flattening, spreading, migrating, and repolarizing of differentiated columnar epithelial cells but is independent of cell proliferation (2,6). Defective regulation of early mucosal restitution underlies various critical pathological states such as massive mucosal injury and hemorrhage, delayed wound healing, disruption of epithelial integrity, and epithelial barrier dysfunction (2, 7).…”

Enhanced gut barrier integrity sensitizes colon cancer to immune therapy

“…It is well known that disruption of gut epithelial barrier can promote tumor growth via complex multi-pathway inflammatory processes that involve both microbial as well as non-microbial factors. 32,33 Specifically, both type 17 and type 1 T-cell activity, as well as innate inflammatory cells can contribute to tumor growth in the inflamed gut. 32,33 In the case of the APC min/+ / B fragilis model microbially-driven type 17 immunity has been shown to be essential to tumor development.…”

“…32,33 Specifically, both type 17 and type 1 T-cell activity, as well as innate inflammatory cells can contribute to tumor growth in the inflamed gut. 32,33 In the case of the APC min/+ / B fragilis model microbially-driven type 17 immunity has been shown to be essential to tumor development. 8,22,34 While our findings are consistent with this paradigm, the ability of IL-12 to exacerbate disease without significant impact on Th17 cells suggests that additional, yet unidentified, factors that are associated with increased gut permeability may also contribute to tumor pathogenesis in this model.…”