Integrin regulation of lymphocyte trafficking: lessons from structural and signaling studies

High trafficking capability of lymphocytes is crucial in immune surveillance and antigen responses. Central to this regulatory process is a dynamic control of lymphocyte adhesion behavior regulated by chemokines and adhesion receptors such as integrins. Modulation of lymphocyte adhesive responses occurs in a wide range of time window from less than a second to hours, enabling rolling lymphocyte to attach to and migrate through endothelium and interact with antigen-presenting cells. While there has been a rapid progress in the understanding of integrin structure, elucidation of signaling events to relay extracellular signaling to integrins in physiological contexts has recently emerged from studies using gene-targeting and gene-silencing technique. Regulatory molecules critical for integrin activity control distribution of integrins, polarized cell morphology and motility, suggesting a signaling network that coordinates integrin function with lymphocyte migration. Here, I review recent studies of integrin structural changes and intracellular signal molecules that trigger integrin activation (inside-out signals), and discuss molecular mechanisms that control lymphocyte integrins and how inside-out signals coordinately modulate adhesive reactions and cell shape and migration.