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Biased agonists of GPR84 and insights into biological control
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  • Vincent Luscombe,
  • Pinqi Wang,
  • Angela Russell,
  • David Greaves
Vincent Luscombe
Oxford University
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Pinqi Wang
Oxford University
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Angela Russell
University of Oxford
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David Greaves
Oxford University

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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.
06 Sep 2023Submitted to British Journal of Pharmacology
07 Sep 2023Assigned to Editor
07 Sep 2023Submission Checks Completed
04 Oct 2023Reviewer(s) Assigned
05 Oct 2023Review(s) Completed, Editorial Evaluation Pending
10 Oct 2023Editorial Decision: Revise Minor