Function and regulation of GPR84 in human neutrophils

Br J Pharmacol. 2024 May;181(10):1536-1549. doi: 10.1111/bph.16066. Epub 2023 Mar 27.

Abstract

Human neutrophils are components of the innate immune system and are the most abundant white blood cells in the circulation. They are professional phagocytes and express several G protein-coupled receptors (GPCRs), which are essential for proper neutrophil functions. So far, the two formyl peptide receptors, FPR1 and FPR2, have been the most extensively studied group of neutrophil GPCRs, but recently, a new group, the free fatty acid (FFA) receptors, has attracted growing attention. Neutrophils express two FFA receptors, GPR84 and FFA2, which sense medium- and short-chain fatty acids respectively, and display similar activation profiles. The exact pathophysiological role of GPR84 is not yet fully understood, but it is generally regarded as a pro-inflammatory receptor that mediates neutrophil activation. In this review, we summarize current knowledge of how GPR84 affects human neutrophil functions and discuss the regulatory mechanisms that control these responses, focusing on the similarities and differences in comparison to the two FPRs and FFA2. LINKED ARTICLES: This article is part of a themed issue GPR84 Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc.

Keywords: GPCR; GPR84; NADPH oxidase; chemotaxis; inflammation; neutrophil; signalling.

Publication types

  • Review

MeSH terms

  • Humans
  • Neutrophils*
  • Phagocytes
  • Receptors, Formyl Peptide
  • Receptors, G-Protein-Coupled
  • Signal Transduction*

Substances

  • Receptors, Formyl Peptide
  • GPR84 protein, human
  • Receptors, G-Protein-Coupled