ICAMs in Immunity, Intercellular Adhesion and Communication

Interactions among leukocytes and leukocytes with immune-associated auxiliary cells represent an essential feature of the immune response that requires the involvement of cell adhesion molecules (CAMs). In the immune system, CAMs include a wide range of members pertaining to different structural and functional families involved in cell development, activation, differentiation and migration. Among them, β₂ integrins (LFA-1, Mac-1, p150,95 and α_Dβ₂) are predominantly involved in homotypic and heterotypic leukocyte adhesion. β2 integrins bind to intercellular (I)CAMs, actin cytoskeleton-linked receptors belonging to immunoglobulin superfamily (IgSF)-CAMs expressed by leukocytes and vascular endothelial cells, enabling leukocyte activation and transendothelial migration. β2 integrins have long been viewed as the most important ICAMs partners, propagating intracellular signalling from β2 integrin-ICAM adhesion receptor interaction. In this review, we present previous evidence from pioneering studies and more recent findings supporting an important role for ICAMs in signal transduction. We also discuss the contribution of immune ICAMs (ICAM-1, -2, and -3) to reciprocal cell signalling and function in processes in which β2 integrins supposedly take the lead, paying particular attention to T cell activation, differentiation and migration.