Interleukin‐10 and interferon‐γ modulate surface expression of fractalkine‐receptor (CX3CR1) via PI3K in monocytes

The membrane‐anchored form of the chemokine fractalkine (CX₃CL1) has been identified as a novel adhesion molecule that interacts with its specific receptor (CX₃CR1) expressed in monocytes, T cells and natural killer cells to induce adhesion. In addition, CX₃CL1 can be cleaved from the cell membrane to induce chemotaxis of CX₃CR1‐expressing leucocytes. Recently, marked variations in CX₃CR1 monocyte expression have been observed during several pathological conditions. Regulation of CX₃CR1 in monocytes during basal or inflammatory/anti‐inflammatory conditions is poorly understood. The aim of this study was therefore to examine CX₃CR1 expression during monocyte maturation and the effect of soluble mediators on this process. We found that basal expression of CX₃CR1 in fresh monocytes was reduced during culture, and that lipopolysacchairde accelerated this effect. In contrast, interleukin‐10 and interferon‐γ treatment abrogated CX₃CR1 down‐modulation, through a phosphatidylinositol 3 kinase‐dependent pathway. Most importantly, CX₃CR1 membrane expression correlated with monocyte CX₃CL1‐dependent function. Taken together, our data demonstrate that CX₃CR1 expression in monocytes can be modulated, and suggest that alterations in their environment are able to influence CX₃CL1‐dependent functions, such as chemotaxis and adhesion, leading to changes in the kinetics, composition and/or functional status of the leucocyte infiltrate.