TY - JOUR
T1 - Pro-lymphangiogenic properties of IFN-γ-activated human dendritic cells
AU - Gagliostro, Vincenzo
AU - Seeger, Pascal
AU - Garrafa, Emirena
AU - Salvi, Valentina
AU - Bresciani, Roberto
AU - Bosisio, Daniela
AU - Sozzani, Silvano
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Cytokines
KW - LEC
KW - NK cells
KW - VEGF-C
UR - http://www.scopus.com/inward/record.url?scp=84961188292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961188292&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2016.03.008
DO - 10.1016/j.imlet.2016.03.008
M3 - Article
AN - SCOPUS:84961188292
VL - 173
SP - 26
EP - 35
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
ER -