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

Abstract

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:

• adhesion molecules
• barrier
• cell migration
• epithelial cells
• neutrophils

Abbreviations:

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

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

This work was supported in part by grants from the NIH (DK072564, DK061379, DK079392 to CP, and DK0167501 to RS).