AbstractArrest chemokines are a small group of chemokines that promote leukocyte arrest from rolling by triggering rapid integrin activation. Arrest chemokines have been described for neutrophils, monocytes, eosinophils, naïve lymphocytes and effector memory T cells. Most arrest chemokines are immobilized on the endothelial surface by binding to heparin sulfate proteoglycans. Many aspects of the signaling pathway from the GPCR chemokine receptor to integrin activation are the subject of active investigation. Leukocyte adhesion deficiency III is a human disease in which chemokine-triggered integrin activation is defective because of a mutation in the cytoskeletal protein kindlin-3. About 10 different such mutations have been described. The defects seen in patients with LAD-III elucidate the importance of rapid integrin activation for host defense in humans. This editorial is intended to introduce the nine articles that are part of this Topic in Frontiers in Immunology.  Chemokines are a large family (~50 members) of chemoattractants that bind to cognate chemokine receptors (~25 known). Leukocytes roll along the vascular endothelium through selectins interacting with their glycoprotein ligands until they encounter a chemokine that stops them in their tracks (1,2). The fact that chemokines can induce arrest of rolling leukocytes and make them adhere was discovered in the 1990’s (3-6), and the term “arrest chemokines” was coined in 2003 (7). Many chemokines including CXCL1, 2, 8, 9, 10, 12, CCL 3, 5, 11, 19, 21 and CX3CL1 have been shown to activate leukocyte integrins and induce arrest, but other chemokines may also have this ability and simply have not been tested in rolling-to-arrest assays. In this eBook, 26 authors have contributed nine articles touching on many of the known arrest chemokines. This eBook is aimed at covering the structure, expression and physiological function of arrest chemokines, the biophysical processes associated with leukocyte arrest and the molecular mechanisms of rapid leukocyte integrin activation responsible for arrest. Bongrand’s group has pioneered the study of the biomechanics of cell adhesion for the past 30 years (8). In their contribution to this eBook (9), they discuss the finite time required for integrin activation, the nanoscale dynamics of the arrest process, and the contribution of local membrane deformation. They apply this knowledge of the biomechanics of leukocyte arrest to the study of the leukocyte arrest defect seen in patients with leukocyte adhesion deficiency (LAD) type III. In this disorder, the cytoskeletal protein kindlin-3 is not expressed and integrin activation is impaired.Once rolling leukocytes encounter immobilized or soluble chemokine, a series of signaling events is triggered that ultimately results in integrin activation by conformational extension, affinity increase and clustering. The proximal signaling is clear: The chemokine binds its G-protein coupled receptor and the Gα subunit dissociates from Gβγ. The distal signaling is also fairly clear: both talin-1 and kindlin-3 bind to the cytoplasmic domain of the β chain of the leukocyte integrin responsible for arrest. But what links the two processes is an area of active investigation. Laudanna and colleagues focus on the roles Rap1 and RhoA, two of many small G proteins found in leukocytes (10).Another signaling paper in this eBook focuses on calcium. Intracellular free calcium rises rapidly when a chemokine binds its receptor, because the dissociated Gβγ subunit of chemokine receptors can trigger calcium release from intracellular stores by activating phospholipase C (PLC)β. It has long been known that arrest is associated with a rise in intracellular …