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

Abstract

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.

Increased Expression of CD169 on Monocytes in Adult-Onset Kikuchi–Fujimoto Disease

“…CD169, a member of the Siglec family, is expressed on the surfaces of specific subsets of macrophages, precursor monocytes and DCs. It contributes to cell-cell adhesion and cell-pathogen interactions since it has high affinity for α2 3 glycosyltransferase and glucosidase and communicates with other immune cells by binding to other cell-surface polysaccharides (e.g., CD43 on T cells) [42,43]. The expression of CD169 is induced on monocytes upon stimulation via type I INF pathways [14] and is associated with higher co-expression levels of co-stimulatory and HLA molecules, suggesting an increased activation state [44].…”