Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

Circulating monocytes (Mos) may continuously repopulate macrophage (MAC) or dendritic cell (DC) populations to maintain homeostasis. MACs and DCs are specialized cells that play different and complementary immunological functions. Accordingly, they present distinct migratory properties. Specifically, whereas MACs largely remain in tissues, DCs are capable of migrating from peripheral tissues to lymphoid organs. The aim of this work was to analyze the expression of the fractalkine receptor (CX₃CR1) during the monocytic differentiation process. Freshly isolated Mos express high levels of both CX₃CR1 mRNA and protein. During the Mo differentiation process, CX₃CR1 is downregulated in both DCs and MACs. However, MACs showed significantly higher CX₃CR1 expression levels than did DC. We also observed an antagonistic CX₃CR1 regulation by interferon (IFN)-γ and interleukin (IL)-4 during MAC activation through the classical and alternative MAC pathways, respectively. IFN-γ inhibited the loss of CX₃CR1, but IL-4 induced it. Additionally, we demonstrated an association between CX₃CR1 expression and apoptosis prevention by soluble fractalkine (sCX₃CL1) in Mos, DCs and MACs. This is the first report demonstrating sequential and differential CX₃CR1 modulation during Mo differentiation. Most importantly, we demonstrated a functional link between CX₃CR1 expression and cell survival in the presence of sCX₃CL1.