Emerging aspects of leukocyte migration

Based on fundamental experiments of the past two decades, the mechanisms that regulate egress of immune cells from blood to lymphoid and nonlymphoid tissue are largely understood. In contrast, hardly anything is known regarding the homing of afferent lymph-derived cells to lymphoid organs. This open field requires further investigation since many of the fundamental processes of immunology, such as DC mobilization from the peripheral organs to the draining lymph nodes, rely on this trafficking route. New imaging techniques like 2-photon and light-sheet microscopy will be of profound value in gaining a better understanding of the molecular and cellular mechanisms that regulate immune cell trafficking from and to the bloodstream as well as the lymphatic system. The selective interference with immune cell homing or egress to or from defined lymphoid and nonlymphoid organs offers new therapeutic strategies to dampen chronic inflammatory processes. Several biologics, in particular those directed against different integrins and selectins, are currently being tested in clinical trials and show very promising results. Although belonging to the large and frequently therapeutically targeted family of G protein-coupled receptors, the therapeutic potential of targeting chemoattractant receptors is still largely unexploited. Clearly, further studies are needed to better delineate the capacity of this receptor class as drug targets.