Figure 1. Molecular signaling induced by CD69 engagement. A) Glycosylation-dependent CD69 ligand-mediated signalling. Binding of Gal-1 of human monocyte-derived dendritic cells to CD69 increases the Treg cell differentiation mostly mediated by JAK3/STAT5 activation. S100A8/S100A9 dimers bind to CD69 on T cells, enhancing SOCS3 expression, which reduces STAT3 phosphorylation and promotes Treg cell development. S100A8/S100A9 tetramers bind to CD69 on monocytes, activating STAT3 modulation through SOCS3 expression and reducing the activity of small GTPases, such as Cdc42, RhoA and Rac, and thus monocyte migration. B) OxLDL-CD69 binding and crosslinking of anti-CD69 antibody induce PD-1 expression. The binding of oxLDL to CD69 induces the expression of the nuclear receptors NR4A, the levels of PD-1 and decreases IL-8 and IFN-γ expression. Crosslinking of anti-CD69 antibodies induces the NFAT activation that leads to PD-1 expression. Cyclosporine A inhibits the PD-1 induction by CD69 engagement. This figure was created with BioRender.com.