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

Vincenzo Gagliostro, Pascal Seeger, Emirena Garrafa, Valentina Salvi, Roberto Bresciani, Daniela Bosisio, Silvano Sozzani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)26-35
Number of pages10
JournalImmunology Letters
Volume173
DOIs
Publication statusPublished - May 1 2016

Keywords

  • Angiogenesis
  • Cytokines
  • LEC
  • NK cells
  • VEGF-C

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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