Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules

Biological barriers regulate the passage of cells, pathogens, fluids, nutrients, ions and signalling molecules between anatomical compartments during homeostasis and disease. Yet strategies that allow for reversible therapeutic modulation of these barriers are still in their infancy. The enhancement or protection of natural barriers is desirable in conditions such as acute respiratory distress syndrome or ischaemia-reperfusion injuries, whereas a temporary disruption could facilitate the penetration of drugs across such barriers. This Review discusses the role of sphingosine-1-phosphate receptors in the regulation and protection of biological barriers, and the potential of therapeutic strategies that target this receptor family.