GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA.

ABSTRACT: Rapid neutrophil recruitment to sites of inflammation is crucial for innate immune responses. Here, we reveal that the G-protein-coupled receptor GPR35 is upregulated in activated neutrophils, and it promotes their migration. GPR35-deficient neutrophils are less recruited from blood vessels into inflamed tissue, and the mice are less efficient in clearing peritoneal bacteria. Using a bioassay, we find that serum and activated platelet supernatant stimulate GPR35, and we identify the platelet-derived serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) as a GPR35 ligand. GPR35 function in neutrophil recruitment is strongly dependent on platelets, with the receptor promoting transmigration across platelet-coated endothelium. Mast cells also attract GPR35⁺ cells via 5-HIAA. Mic

SUBMITTER: De Giovanni M 

PROVIDER: S-EPMC9037118 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature