Endothelial and epithelial barriers in graft-versus-host disease.

Endothelial and epithelial cells form selectively permeable barriers that separate tissue compartments. These cells coordinate movement between the lumen and tissue via the transcellular and paracellular pathways. The primary determinant of paracellular permeability is the tight junction, which forms an apical belt-like structure around endothelial and epithelial cells. This chapter discusses endothelial and epithelial barriers in graft-versus-host disease after allogeneic bone marrow transplantation, with a focus on the tight junction and its role in regulating paracellular permeability. Recent studies suggest that in graft-versus-host disease, pathological increases in paracellular permeability, or barrier dysfunction, are initiated by pretransplant conditioning and sustained by alloreactive cells and the proinflammatory milieu. The intestinal epithelium is a significant focus, as it is a target organ of graft-versus-host disease, and the mechanisms of barrier regulation in intestinal epithelium have been well characterized. Finally, we propose a model that incorporates endothelial and epithelial barrier dysfunction in graft-versus-host disease and discuss modulating barrier properties as a therapeutic approach.