Approximately 10% of G protein– coupled receptors are orphans whose ligands await identification. Until now, the lymphocyte-expressed receptor G2A has been one of these orphans. But Yan Xu (Cleveland Clinic Foundation, Cleveland, OH) and Owen Witte (University of California at Los Angeles, CA) and colleagues have just reported that a small lipid, the inflammatory mediator lysophosphatidylcholine (LPC), is a high-affinity G2A ligand.
The finding links together two previously unrelated lines of research on atherosclerosis and inflammatory autoimmune disease, and it begins to suggest mechanisms involved in those disorders. Researchers have known that LPC is important in both atherosclerosis (as a component of oxidized low density lipoprotein [LDL]) and autoimmune diseases such as systemic lupus erythematosus. Witte's lab reported in May that mice lacking the G2A gene develop a progressive wasting disease resembling lupus (Immunity. 14:561)....