Cytokine responses and epithelial function in the intestinal mucosa

Abstract

Inflammatory diseases of mucosal organs are significantly influenced by the microenvironment in which they reside. Cytokines found within this microenvironment contribute significantly to endpoint functions of the mucosa. Studies dating back to the 1990s have revealed that epithelial cells are both a source as well as a target for numerous cytokines and that such signaling can substantially influence the outcome of mucosal disease, such as inflammatory bowel disease. Here, we will review literature regarding intestinal epithelial cells as sources and responders to cytokines found in the intestinal milieu. These studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.

Keywords: Colitis; Epithelium; Inflammation; Leukocyte; Mucosa; Murine model.

Fig. 1

IFN-gamma as a model cytokine signaling hub in the intestinal mucosa: 1 IFN-gamma signaling through basolaterally localized receptors induces the expression of immune regulatory components including MHC class I and II, CD1d as well as the apical IL-10R. 2 Through the down-regulation of CFTR and multiple ion channels in the epithelial membrane, IFN-gamma abrogates electrogenic chloride secretion and associated water transport (see text for details). 3 IFN-gamma signaling increases epithelial permeability through the regulation of tight junction (TJ) and adherens junction (AJ) component expression. 4 IFN-gamma signaling induces the apical expression of ICAM-1 and the basolateral expression of CD47. Together this allows migration and apical localization of neutrophils (PMN)