Abstract
GPR84 was first identified as an open reading frame encoding an orphan
Class A G protein coupled receptor in 2001. Gpr84 mRNA is
expressed in a limited number of cell types with the highest levels of
expression being in innate immune cells, M1 polarised macrophages and
neutrophils. The first reported ligands for this receptor were medium
chain fatty acids with chain lengths between 9 and 12 carbons.
Subsequently a series of synthetic agonists that signal via the GPR84
receptor were identified. Radioligand binding assays and molecular
modelling with site-directed mutagenesis suggest the presence of three
ligand binding sites on the receptor, but the physiological agonist(s)
of the receptor remain unidentified. Here, we review the effects of
GPR84 agonists on innate immune cells following a series of chemical
discoveries since 2001. The development of highly biased agonists has
helped to probe receptor function in vitro , and the challenge
remaining is to follow the effects of biased signalling to the
physiological functions of innate immune cell types.