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Mouse Classical and Non-Classical Monocytes Express Comparable Levels of Chemokine Receptor CX3CR1

Human and mouse monocytes are divided into two subpopulations, classical (C-Mo) and non-classical (NC-Mo) monocytes. CC-chemokine receptor 2 (CCR2) and CX3C-chemokine receptor 1 (CX3CR1) are common features of monocyte subsets between humans and mice, i.e., C-Mo and NC-Mo are characterized as CCR2highCX3CR1low and CCR2lowCX3CR1high. Since many studies utilize mouse models to investigate roles of monocytes in human diseases, it is important to understand the similarities and differences between human and mouse monocytic subsets. In this study, we show that the expression of Cx3cr1 mRNA and CX3CR1 cell surface protein are different between circulating monocytic subsets in human but not in mice. We analyzed monocyte subsets in the blood using wild type C57BL/6 and Cx3cr1-GFP knock-in (Cx3cr1GFP/+) reporter mice. We observed higher Cx3cr1 promoter activity indicated by GFP expression in NC-Mo compared to C-Mo. However, there were no differences between the subsets in CX3CR1 mRNA nor surface protein expression determined by anti-CX3CR1 antibody or binding of fluorophore-conjugated ligand. However in the bone marrow of Cx3cr1GFP/+ mice, CX3CR1 expression was higher in NC-Mo compared to C-Mo, suggesting that mouse NC-Mo express higher level of CX3CR1 than C-Mo in the bone but this difference disappears in the blood. In contrast, human NC-Mo differentially expressed CX3CR1 compared to C-Mo in both blood and bone marrow. Given these findings, the discrepancy between promoter activity and protein levels should be considered when the roles of CX3CR1 are investigated in mouse models of human diseases. Summary sentence In this study, we show that the expression of Cx3cr1 mRNA is different between circulating monocytic subsets in human but not in mice.