title: Pro-lymphangiogenic properties of IFN-γ-activated human dendritic cells.
abstract: Dendritic cells (DCs) play a crucial role in the initiation of adaptive immune responses. In addition, 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 produce VEGF-C, a cytokine with potent pro-lymphangiogenic activity when stimulated with IFN-γ. 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-γ 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.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gagliostro
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Pascal
authors.initials: P
authors.lastname: Seeger
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Emirena
authors.initials: E
authors.lastname: Garrafa
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salvi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bresciani
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bosisio
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Humanitas Clinical Research Center, Rozzano, Italy. Electronic address: silvano.sozzani@unibs.it.
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
mesh_terms: D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000502:physiology*; D004729:Endothelium, Lymphatic / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D019409:Interleukin-15; D042582:Vascular Endothelial Growth Factor C; D007371:Interferon-gamma
keywords: Angiogenesis; Cytokines; LEC; NK cells; VEGF-C