Just like classical chemokine receptors, atypical chemokine receptors (ACKRs) are seven-transmembrane-helix (7TM) receptors that bind chemokines []. However, they lack the canonical DRYLAIV motif necessary for GPCR coupling to G proteins and induction of classical signalling pathways. Instead, ACKRs internalise their chemokine ligands, which may subsequently affect chemokine availability. The ACKR family comprises five members: Duffy Antigen Receptor for Chemokines (DARC, ACKR1), D6 (ACKR2), CXCR7 (ACKR3), CCRL1 (ACKR4) and CCRL2 (ACKR5) [].Atypical chemokine receptor 4 (ACKR4/CCRL1/CCX-CKR) binds and scavenges the ligands of the chemokine receptors CCR7 and CCR9 (CCL19/CCL21 and CCL25, respectively) and targets them for subsequent lysosomal degradation [, ]. Apart from being a scavenger for chemokines, it may prevent CXCR3-induced chemotaxis by heteromerisation []. ACKR4 appears to have a mayor role in normal thymus development and function [].
