The Role of Membrane Lipids in the Regulation of Immune Cell Activity

Engagement of immune receptors by antigen triggers processes that culminate in activation, cell proliferation, differentiation and effector functions. A growing body of evidence suggests that it is within specialized membrane regions called lipid rafts that the initiation and propagation of the signaling events taking place in immune cells occurs. These specialized membrane compartments are enriched in cholesterol and glycolipids and contain many lipid-modified signaling proteins such as GPI (glycosylphosphatidylinositol)- linked proteins, Src family tyrosine kinases and other adaptor proteins. By confining certain signaling molecules in membrane subdomains, lipid rafts have been proposed to function as platforms for the formation of multi-unit transduction complexes. Therefore, it has been suggested that the translocation of immune receptors into lipid rafts regulates immune cell activation. In lymphocytes it has been shown that immune receptors become lipid raft-associated upon antigen cross-linking, and signaling complexes are formed when additional components of the signaling pathways are recruited to lipid rafts. Furthermore, substantial evidence from a number of experiments shows that the integrity of lipid rafts is crucial for the initiation and maintenance of intracellular signals. Recent studies have also shown that the access and translocation of immune receptors to lipid rafts are developmentally regulated (immature versus mature cells, naïve versus effector) and that the cholesterol content plays an important role in maintaining plasma membrane heterogeneity and influencing a variety of cellular processes including signaling, adhesion, and permeability. The aim of this review is to examine the role membrane lipids play in regulating immune activation.