Diacylglycerol kinases put the brakes on immune function

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 important role in limiting the immune response. Other studies have examined the molecular basis of anergy, a state of T cell unresponsiveness that is an important postdevelopmental control over the immune response to self antigens. Two groups have suggested that DGK activity lies at the heart of the anergic phenotype. In addition, DGK activity may limit the response of macrophages and dendritic cells to intracellular pathogens. An overall picture is emerging in which the capacity of DGKs to modulate membrane signaling lipids is used to keep a tight rein on immune responses.