The human and the murine GPR84 ORFs both encode proteins of 396 amino acid residues length with 85% identity and are therefore considered as orthologs. and adipocytes. A more detailed description of expression profile can be found in www.genecards.org. The resting expression of GPR84 is usually low but it is highly inducible in inflammation. Its expression on neutrophils can be increased with
LPS stimulation and reduced with
GM-CSF stimulation. The LPS-induced upregulation of GPR84 was not sensitive to dexamathasone pretreatment. There was also a GPR84 downregulation in dentritic cell derived from FcRgamma chain KO mice. In microglial cells, the GPR84 induction with
interleukin-1 (IL-1) and
tumor necrosis factor α (TNFα) was also demonstrated. While another publication suggests that GPR84 is rather a CCL1 related Th2 type gene. GPR84 was also upregulated on both macrophages and neutrophyl granulocytes after
LPS stimulation. Not only
LPS challenge but
Staphylococcus enterotoxin B was sufficient to cause a 50 times increase in GPR84 expression on isolated human
leukocytes stimulated with compared to the expression of naive leukocytes. A viral infection following Japanese encephalitis virus infection also increased GPR84 expression by 2–4.5% in the mice brain. Ablating
lysosomal acid lipase (Lal-/-) in mice led to aberrant expansion of
myeloid-derived suppressive cells (MDSCs) (>40% in the blood, and >70% in the bone marrow) that arise from dysregulated production of myeloid progenitor cells in the bone marrow. Ly6G + MDSCs in Lal-/- mice show strong immunosuppression on T cells, which contributes to impaired T cell proliferation and function in vivo. GPR84 was 9.1 fold upregulated in the MDSCs of Lal-/- mice. GPR84 is normally expressed at low levels in myeloid cells and can be induced in vitro by stimulating macrophage or microglial cells with LPS, TNFα, or PMA. Elevated expression of GPR84 was also observed during the demyelination phase of the reversible Cuprizone-Induced Demyelinating Disease mouse model. Finally, it has also shown that GPR84 expression is increased in both the normal appearing white matter and plaque in brains from human Multiple Sclerosis patients. Expression of GPR84 increases in mouse whole brain samples from
experimental autoimmune encephalomyelitis before the onset of clinical disease. In cultured microglia in response to simulated blast overpressure the expression of GPR84 was increased 2.9 fold. In ageing TgSwe mice were subjected to traumatic brain injury GPR84 was upregulated by 6.3 fold. GPR84 expression was increased by 49.9 times in M1 type macrophages isolated from aortic atherosclerotic lesions of LDLR-/- mice were fed a western diet. GPR84 is important in regulating the expression of cytokines: CD4+ T cells from GPR84-/- mice show increase IL-4 secretion in the presence of anti-CD3 and anti-CD28 antibodies; GPR84 potentiates LPS-induced IL12p40 secretion in RAW264.7 cells. Recent work by Nagasaki et al. explored 3T3-L1 adipocytes cocultured with RAW264.7 cells to examine this potential interaction. == Ligands ==