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  • Phagocytosis was observed at min after mixing macrophages wi


    Phagocytosis was observed at 60 min after mixing macrophages with microbes (A). The phagocytosis ability (PA) and phagocytosis index (PI) values of the macrophages engulfing the bacteria measured in flow cytometer were shown in histograms (B). Statistical analyses revealed that both the PA and PI values in zebrafish -overexpression macrophages engulfing were significantly increased compared with those of the cells transfected with pcDNA3.1/V5-His vector alone (C). Similarly, both the PA and PI values in zebrafish -overexpression macrophages engulfing were also markedly elevated compared with those of the cells transfected with pcDNA3.1/V5-His vector alone (C). Collectively, these suggested that zebrafish Gpr84 was able to promote the phagocytosis of bacteria by the macrophages. The study expands our understanding of the role of zebrafish Gpr84 in immune reaction. Conflicts of interest
    Acknowledgements This work was supported by the grants of National Natural Science Foundation of China (31572259) and the Fundamental Research Funds for the Central Universities (201762003).
    Introduction A large number of GPCRs are expressed on cells of immune origin where they modulate cell functions such as migration, production of inflammatory mediators, proliferation, regulation of apoptosis and others. Among these are several receptors that are either orphan, with as yet unidentified natural ligands, or whose role in regulation of cellular functions has not been fully elucidated. One such receptor is GPR84, a GPCR that was originally cloned from a human granulocyte cDNA library [1] and also identified in expressed sequence tag data mining studies [2]. GPR84 has no close homologs, the closest homology being to the dopamine D2 receptor with only 26% amino metforman identity, and is highly conserved between human and rodents, with 85% identity between human and mouse receptors. The receptor is almost exclusively expressed in immune cells or tissues rich in cells of immune origin, including lung, bone marrow, peripheral blood leucocytes and microglia [[1], [2], [3]]. GPR84 expression has been shown to be upregulated upon stimulation of immune cells by inflammatory stimuli such as LPS, TNFα and others [[4], [5], [6]]. In mouse models of endotoxemia and experimental autoimmune encephalomyelitis (EAE) GPR84 expression on microglia is drastically upregulated [4]. In a mouse model of neuropathic pain, elevated GPR84 expression in sciatic nerve and spinal cord has been observed, presumably on microglial cells [7]. Although GPR84 expression outside of the immune system is rare, one notable exception is a report of receptor expression on 3T3-L1 adipocytes following treatment with TNFα, where it is claimed to be involved in regulation of adiponectin levels [8]. Medium chain fatty acids have been reported to activate GPR84 and initiate Gi/o signaling in recombinant cells [5], though their function as physiological/natural ligands for GPR84 has not been confirmed. Since its identification there have been few reports on the physiological function of GPR84. Knock-out of GPR84 leads to an increase of Th2 cytokines (IL-4, IL-5, IL-13) in mouse CD4+ T lymphocytes [3]. In leukemic stem cells, GPR84 maintains β-catenin signaling important for acute myeloid leukemia (AML) maintenance [9]. Some published reports suggest that GPR84 activation leads to certain proinflammatory phenotypes. In RAW264.7 cells, a mouse macrophage-like cell line, GPR84 activation increases production of IL-12, a cytokine involved in the Th1/Th2 balance of T helper responses [5]. Putative GPR84 ligands have been shown to induce chemotaxis and stimulate production of IL-8 from PMNs, as well as TNFα from macrophages [10]. Similarly, macrophages derived from GPR84 knock-out cells exhibited decreased production of several proinflammatory mediators, such as IL-1β, IL-6 and TNFα upon stimulation with lipopolysaccharide [7]. In a neuropathic pain model, loss of GPR84 leads to significantly reduced development of thermal hypersensitivity, possibly due to the absence of GPR84-mediated release of proinflammatory mediators [7].