Regulation of immunity by lysosphingolipids and their G protein-coupled receptors

T and B lymphocytes, as well as endothelial cells, express distinctive profiles of G protein-coupled receptors for sphingosine 1-phosphate, which is a major regulator of T cell development, B and T cell recirculation, tissue homing patterns, and chemotactic responses to chemokines. The capacity of drugs that act on type 1 sphingosine 1-phosphate receptors to suppress organ graft rejection in humans and autoimmunity in animal models without apparent impairment of host defenses against infections suggests that this system is a promising target for new forms of immunotherapy.