Regulation of the intestinal epithelial barrier by the apical junctional complex.
OBJECTIVE
Epithelial intercellular junctions are important components of the epithelial barrier and are compromised in disorders such as Crohn's disease. We will highlight recent progress in understanding the role of an intercellular junction referred to as the apical junctional complex in regulating small intestinal epithelial permeability in health and disease.


RESULTS
Recent studies have implicated aberrant regulation of the AJC as an underlying factor contributing to a leaky epithelial barrier in Crohn's patients. Consequences of increased epithelial permeability include exposure of intestinal tissue to luminal antigens/pathogens which in turn influence disease activity. Furthermore, proinflammatory cytokines released into the milieu of the epithelium in patients with Crohn's disease influence apical junctional complex and epithelial barrier function. Such cytokines induce disassembly of the apical junctional complex by promoting differential endocytosis of component proteins. Additionally, apical junctional complex proteins are targeted by pathogens that use the epithelium as a portal of entry to establish disease in the host.


CONCLUSIONS
The epithelial apical junctional complex is important in determining epithelial barrier properties. Recent studies have highlighted contribution of proinflammatory cytokines and endocytosis of apical junctional complex proteins to the epithelial barrier defect. Continued advances in understanding of this field will yield new therapeutic targets for intestinal disorders.
Laukoetter
Mike G
MG
Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Bruewer
Matthias
M
Nusrat
Asma
A
D022005:Adherens Junctions / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*
D016207:Cytokines