GPR84

GPR84 Full Name

G protein-coupled receptor 84

GPR84 Introduction

GPR84 is an orphan class A G protein-coupled receptor that has been deorphanized as a receptor for medium-chain fatty acids, with capric acid (C10), lauric acid (C12), and related hydroxylated lipids identified as the most potent agonists. It is expressed predominantly on myeloid cells—neutrophils, monocytes, macrophages, and microglia—where its levels are strongly induced by inflammatory stimuli, but it is also detectable in adipocytes and certain epithelial populations. The gene maps to human chromosome 12q13.13, and the receptor couples predominantly to Gαi/o proteins to inhibit adenylate cyclase and elevate intracellular calcium.

Figure 1. The structure of GPR84.

Myeloid Cell Chemotaxis and Inflammatory Signaling
Ligand binding to GPR84 activates Gαi, leading to inhibition of cAMP accumulation, activation of PI3K and Akt, and downstream engagement of the MAPK cascade. In neutrophils and macrophages, GPR84 signals through β-arrestin 2 and Gαi to amplify chemotaxis toward inflammatory foci, sustain NADPH-oxidase activity, and delay apoptosis, thereby prolonging the effector phase of innate immune responses. In microglia, GPR84 senses the lipid-rich milieu of damaged brain tissue and contributes to microglial activation in models of neuroinflammation; in adipocytes, it modulates lipolysis and the secretion of inflammatory adipokines.

Inflammatory Bowel Disease, Neuroinflammation, and Metabolic Dysfunction
GPR84 expression is markedly elevated in colonic biopsies from patients with ulcerative colitis and Crohn disease, and small-molecule GPR84 antagonists reduce leukocyte infiltration and tissue damage in murine colitis models. In Alzheimer disease and multiple sclerosis, microglial GPR84 expression correlates with neuroinflammatory burden, and pharmacological GPR84 blockade has shown benefit in mouse models of EAE. Metabolic studies further link GPR84 to obesity-associated inflammation, with receptor activation in adipose tissue promoting a pro-inflammatory macrophage phenotype that worsens insulin resistance.

Alternate Names for GPR84

GPR84; G protein-coupled receptor 84; EX33; GPCR4; G-protein coupled receptor 84; inflammation-related G protein-coupled receptor EX33; inflammation-related G-protein coupled receptor EX33;