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

The monocyte adhesion to endothelial cells is an early step in chronic inflammation. Interferon-γ (IFN-γ) is regarded as a master regulator of inflammation development. However, the significance of IFN-γ in the monocyte adhesion to endothelial cells remains largely unknown. In this study, we found that IFN-γ increased PD-L1 transcription in endothelial cells through IRF-1 transcription factor, and subsequently enhanced the adhesion of monocyte to endothelial cells. PD-L1 in endothelial cells interacted with CD169/Siglec 1 in monocyte depending on the α2,3-sialylation of PD-L1. ST3Gal4 (ST3β-galactoside α-2,3-sialyltransferase 4) was the major glycosyltransferase responsible for the α2,3-sialylation of PD-L1. Down-regulation of α2,3-sialylation of PD-L1 by ST3Gal4 knockdown reduced the PD-L1-CD169 interaction. Purified PD-L1 protein with α2,3-sialylation, but not PD-L1 protein without α2,3-sialylation, reduced IFN-γ-induced monocytes adhesion to endothelial cells. Collectively, the interaction between PD-L1 and CD169 promoted monocytes adhesion to endothelial cells. Our findings provide a new mechanism of monocytes adhesion to endothelial cells.