Gpr84-flox Mouse

Gpr84, a G protein-coupled receptor, is a medium-chain fatty acid receptor. It is involved in multiple biological processes, with its activation being largely pro-inflammatory. It is expressed in innate immune cells such as neutrophils, monocytes, macrophages, and myeloid-derived suppressor cells (MDSCs), and is associated with inflammatory and metabolic pathways [3,6,7]. Gene knockout mouse models have been crucial for studying Gpr84.

In acute lung injury (ALI) mouse models, Gpr84 deficiency or blockage significantly alleviated lung inflammation by reducing neutrophil infiltration and oxidative stress. Activation of Gpr84 in neutrophils induced reactive oxygen species production [1]. In brown adipose tissue (BAT) of Gpr84-KO mice, increased lipid accumulation, reduced BAT activity, and mitochondrial dysfunction were observed. The Gpr84 agonist could counteract these effects [2]. Gpr84 -/- mice were resistant to dextran sulfate sodium (DSS)-induced colitis, as Gpr84 activation enhanced NLRP3 inflammasome activation in macrophages [3]. Targeting Gpr84 in MDSCs enhanced anti-PD-1 efficacy in esophageal cancer, as Gpr84 was overexpressed on MDSCs and drove immunosuppression on CD8+T cells [4]. Also, transfer of Gpr84 from MDSCs to CD8+ T cells via exosomes induced T-cell senescence via the p53 signaling pathway [5].

In conclusion, Gpr84 plays essential roles in inflammation, metabolism, and tumor immune regulation. Gene knockout mouse models have revealed its functions in diseases like ALI, metabolic disorders, ulcerative colitis, and esophageal cancer, suggesting it as a potential therapeutic target for these conditions.