Lipid Signaling

The healthy immune system makes use of a variety of surveillance mechanisms at different stages of lymphoid development to prevent the occurrence and expansion of potentially harmful autoreactive T cell clones. Disruption of these mechanisms may lead to inappropriate activation of T cells and the development of autoimmune and lymphoproliferative diseases [such as multiple sclerosis, rheumatoid arthritis, lupus erythematosus, diabetes and autoimmune lymphoproliferative syndrome (ALPS)]. Diacylglycerol kinases (DGKs) are emerging as key negative regulators of immune function, particularly in T cells. DGKs consume diacylglycerol to produce phosphatidic acid. Because both diacylglycerol and phosphatidic acid are important activators of signaling molecules, DGKs have the potential to modulate a number of signaling pathways, and this certainly seems to be the case in T cell function. Studies of T cell signaling demonstrate that DGKs inhibit T cell receptor signaling and thus may serve an imp