Figure 6. Schematic of proposed mechanisms of LEC-mediated dendritic cell modulation.

The VEGF-C-mediated expansion of the inflammatory lymphatic vessel network results in an immune-inhibitory dermal microenvironment. An imbalance in LEC synthesis of prostaglandins, namely a shift towards increased synthesis of the inflammation limiting prostacyclin, concomitant with decreased synthesis of the pro-inflammatory PGE₂, represents a key mechanism resulting in the generation of immature DCs with an anti-inflammatory cytokine profile. These effects are compounded by increased LEC-derived TGF-β1 production. In addition, the dermal cellular milieu exhibits elevated numbers of Tregs. Decreased DC maturation is implicated in the generation of CD8+ T cells with a reduced ability to produce pro-inflammatory IFN-γ.