The role of sphingosine-1-phosphate receptor modulators in the prevention of transplant rejection and autoimmune diseases.
The major sphingolipid metabolite sphingosine-1-phosphate (S1P) plays a central role in maintaining the homeostasis of lymphocyte motility. S1P is the ligand for a family of five GPCRs termed S1P1 to S1P5, each with distinct signaling pathways. The significance of S1P in immune cell regulation was revealed when the immunomodulator fingolimod (Mitsubishi Tanabe Pharma Corp/Novartis AG) was discovered to cause lymphopenia via S1P1 signaling. Clinical trials have targeted S1P1 receptor modulators for autoimmune diseases, particularly for the potential treatment of multiple sclerosis (MS) and the prevention of transplant rejection. This review highlights the potential use of S1P receptor modulation in the clinic and summarizes the clinical experience with these compounds in MS and transplant rejection.
Japtok
Lukasz
L
Freie Universität Berlin, Institute of Pharmacy, Pharmacology and Toxicology, Königin-Luise-Strause 2+4, D-14195 Berlin, Germany.
Kleuser
Burkhard
B
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000503:physiopathology; D002465:Cell Movement; D002986:Clinical Trials as Topic; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D016377:Organ Transplantation / Q000379:methods; D049349:Receptors, Lysosphingolipid / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction
D049349:Receptors, Lysosphingolipid