Allosteric targeting of the FFA2 receptor (GPR43) restores responsiveness of desensitized human neutrophils.

The G protein-coupled free fatty acid receptor 2 (FFA2R) is highly expressed on neutrophils and was previously described to regulate neutrophil activation. Allosteric targeting of G protein-coupled receptors (GPCRs) is increasingly explored to create distinct pharmacology compared to endogenous, orthosteric ligands. The consequence of allosteric versus orthosteric FFA2R activation for neutrophil response, however, is currently largely elusive.