AUTHOR=Melgrati Serena , Gerken Oliver J. , Artinger Marc , Radice Egle , Szpakowska Martyna , Chevigné Andy , D’Uonnolo Giulia , Antonello Paola , Thelen Sylvia , Pelczar Pawel , Legler Daniel F. , Thelen Marcus TITLE=GPR182 is a broadly scavenging atypical chemokine receptor influencing T-independent immunity JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1242531 DOI=10.3389/fimmu.2023.1242531 ISSN=1664-3224 ABSTRACT=
Immune responses highly depend on the effective trafficking of immune cells into and within secondary lymphoid organs (SLOs). Atypical chemokine receptors (ACKRs) scavenge chemokines to eliminate them from the extracellular space, thereby generating gradients that guide leukocytes. In contrast to canonical chemokine receptors, ACKRs do not induce classical intracellular signaling that results in cell migration. Recently, the closest relative of ACKR3, GPR182, has been partially deorphanized as a potential novel ACKR. We confirm and extend previous studies by identifying further ligands that classify GPR182 as a broadly scavenging chemokine receptor. We validate the “atypical” nature of the receptor, wherein canonical G-protein-dependent intracellular signaling is not activated following ligand stimulation. However, β-arrestins are required for ligand-independent internalization and chemokine scavenging whereas the C-terminus is in part dispensable. In the absence of GPR182