International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

On the move: endocytic trafficking in cell migration

“…Here the atypical chemokine CCRL1/ACKR4 expressed by lymphatic endothelial cells lining the ceiling of the subcapsular sinus [11], scavenges CCL21, which is produced by stromal cells in the T zone of lymph nodes [12], to form the chemokine gradient. Additional atypical chemokine receptors have been described, which in contrast to classical chemokine receptors do not transmit signals resulting in chemotaxis [13], however, their role in generating chemokine gradients and their potential regulation by endocytosis have not yet been addressed. In addition, chemokines can be scavenged by classical signal transducing chemokine receptors during cell migration as shown for the inflammatory chemokine CCL2 which is internalized and removed by monocytes during chemotaxis [14].…”

Identification and expression analysis of an atypical chemokine receptor-2 (ACKR2)/CC chemokine binding protein-2 (CCBP2) in rainbow trout (Oncorhynchus mykiss)

“…The coordinated movement of leucocytes is mediated primarily by the chemokine system that includes a large number of ligands binding to a smaller number of receptors [1e3]. For example, the human chemokine system consists of 48 ligands and 23 receptors [1,4]. The chemokine ligands have been classified into four groups (CC, CXC, CX3C, and XC) based on the position of the first two cysteine residues [5e7].…”

“…Chemokine receptors are seven transmembrane molecules connected by three intracellular loops (ICL) and three extracellular loops (ECL), and have a conserved DRY amino acid motif within the second ICL, which is involved in coupling to G-proteins [4,8]. The binding of classic chemokine receptors with their ligands results in multiple signal transduction pathways, triggering a cascade of intracellular events from gene transcription to cytoskeleton rearrangement and chemotaxis [9,10].…”

“…ACKRs serve homeostatic functions by clearing chemokines from the circulation and tissues [1,4,14e16]. ACKR1 binds a large number of CXC and CC inflammatory but not homeostatic chemokines, is abundantly expressed by erythrocytes, and functions as a chemokine sink [1,4]. Human ACKR2 binds at least 12 inflammatory CC chemokines and plays well characterized roles in the regulation of the in vivo inflammatory response [11,12].…”

“…ACKRs influence leukocyte recruitment by 'tuning' the concentrations and gradients of ligands in tissues by diverse means, including binding, storing, scavenging, transporting and trans-presenting chemokines. Thus, ACKRs have emerged as key components of the chemokine system, with an essential regulatory function in innate and adaptive immune responses and inflammation [4].…”