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.