| First Author | De Giovanni M | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 5 | Pages | 815-830.e19 |
| PubMed ID | 35148838 | Mgi Jnum | J:322764 |
| Mgi Id | MGI:7259976 | Doi | 10.1016/j.cell.2022.01.010 |
| Citation | De Giovanni M, et al. (2022) GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA. Cell 185(5):815-830.e19 |
| abstractText | 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. Mice deficient in 5-HIAA show a loss of GPR35-mediated neutrophil recruitment to inflamed tissue. These findings identify 5-HIAA as a GPR35 ligand and neutrophil chemoattractant and establish a role for platelet- and mast cell-produced 5-HIAA in cell recruitment to the sites of inflammation and bacterial clearance. |
