Sialylation-dependent interaction between PD-L1 and CD169 promotes monocytes adhesion to endothelial cells

The monocytes adhesion to endothelial cells is an early step in chronic inflammation. Interferon-gamma (IFN-gamma) is regarded as a master regulator of inflammation development. However, the significance and mechanisms of IFN-gamma in the monocyte adhesion to endothelial cells remains largely unknown. IFN-gamma up-regulates PD-L1 on various types of cells. Here, we performed flow cytometry to examine the contribution of IFN-gamma-induced PD-L1 expression on the monocytes adhesion to endothelial cells. Up-regulation of PD-L1 by IFN-gamma enhanced the adhesion of monocytes to endothelial cells. By immunoprecipitation and lectin blot, PD-L1 in endothelial cells interacted with CD169/Siglec 1 in monocyte depending on the alpha 2,3-sialylation of PD-L1. ST3Gal family (ST3 beta-galactoside alpha-2,3-sialyltransferase) was the major glycosyltransferase responsible for the alpha 2,3-sialylation of membranes proteins. Down-regulation of ST3Gal4 by RNAinterference partially reduced the alpha 2,3-sialylation of PD-L1 and the PD-L1-CD169 interaction. Finally, purified PD-L1 protein with alpha 2,3-sialylation, but not PD-L1 protein without alpha 2,3-sialylation, partially reduced IFN-gamma-induced monocytes adhesion to endothelial cells. These findings provide evidence that the interaction between PD-L1 and CD169 promoted monocytes adhesion to endothelial cells and might elucidate a new mechanism of monocytes adhesion to endothelial cells.