Pro-lymphangiogenic properties of IFN-γ-activated human dendritic cells

Dendritic cells (DCs)play a crucial role inthe initiationof adaptive immune responses.Inaddition,through the release of pro- and anti-angiogenic mediators, DCs are key regulators of blood vessel remodeling, a process that characterizes inflammation. Less information is available on the role of DCs in lymphangiogenesis. This study reports that human DCs produceVEGF-C, a cytokine with potent pro-lymphangiogenic activity when stimulated with IFN-. DC-derived VEGF-C was biologically active, being able to promote tube-like structure formation in cultures of human lymphatic endothelial cells (LECs). DCs co-cultured with IL-15-activated NK cells produced high levels of VEGF-C, suggesting a role for NK-DC cross-talk in peripheral lymphoid and non-lymphoid tissues in inflammation-associated lymphangiogenesis. Induction of VEGF-C by IFN- was detected also in other myeloid cells, such as blood-purified CD1c+ DCs, CD14+ monocytes and in monocyte-derived macrophages. In all these cell types, VEGF-C was found associated with the cell membrane by low affinity, heparan sulphate-mediated, interactions. Therefore, human DCs should be considered as new players in inflammation-associated lymphangiogenesis.