Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration

Tissue Barriers. 2015 Apr 3;3(1-2):e969100. doi: 10.4161/21688362.2014.969100. eCollection 2015.


Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from the surrounding tissue. Others serve as docking structures for invading viruses and bacteria, while also regulating the immune response. They can either obstruct or serve as footholds for the immune cells recruited to mucosal surfaces. Currently, it is well appreciated that adhesion molecules collectively serve as environmental cue sensors and trigger signaling events to regulate epithelial function through their association with the cell cytoskeleton and various intracellular adapter proteins. Immune cells, particularly neutrophils (PMN) during transepithelial migration (TEM), can modulate adhesion molecule expression, conformation, and distribution, significantly impacting epithelial function and tissue homeostasis. This review discusses the roles of key intestinal epithelial adhesion molecules in regulating PMN trafficking and outlines the potential consequences on epithelial function.

Keywords: AJs, adherens junctions; CAR, coxsackie and adenovirus receptor; CLMP, CAR-like protein; CTLs, cytotoxic T lymphocytes; CTX, thymocyte Xenopus; DMs, Desmosomes; Dsc-2, desmocollin-2; Dsg-2, desmoglein-2; E-cadherin, epithelial cadherin; EGFR, Epithelial growth factor receptor; EMT, epithelial-mesenchymal transition; EpCAM, epithelial cell adhesion molecule; IBD, inflammatory bowel diseases; ICAM-1, intercellular adhesion molecule-1; IECs, intestinal epithelial cells; JAM, junctional adhesion molecules; LAD, leukocyte adhesion deficiency; LTB-4, lipid leukotriene B4; MIP1 α, macrophage inflammatory protein 1 alpha; MLCK, myosin light chain kinase; MMPs, matrix metalloproteases; NF-κB, nuclear factor kappa B; NO, nitric oxide; PARS, protease-activated receptors; PI3K, phosphatidylinositol 3-kinase; PMN, polymorphonuclear cells; SGD, specific granule deficiency; SIRPa, signal regulatory protein alpha; TEM, transepithelial migration; TGF-β, transforming growth factor beta; TIAM1, metastasis-inducing protein 1; TJs, tight junctions; TSP-1, thrombospondin-1; adhesion molecules; barrier; cell migration; epithelial cells; neutrophils; sLea, sialyl Lewis A.