PMID- 26987844 OWN - NLM STAT- MEDLINE DCOM- 20171016 LR - 20171113 IS - 1879-0542 (Electronic) IS - 0165-2478 (Linking) VI - 173 DP - 2016 May TI - Pro-lymphangiogenic properties of IFN-gamma-activated human dendritic cells. PG - 26-35 LID - S0165-2478(16)30033-5 [pii] LID - 10.1016/j.imlet.2016.03.008 [doi] 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-gamma. 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-gamma 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. CI - Copyright (c) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. FAU - Gagliostro, Vincenzo AU - Gagliostro V AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Seeger, Pascal AU - Seeger P AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Garrafa, Emirena AU - Garrafa E AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Salvi, Valentina AU - Salvi V AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Bresciani, Roberto AU - Bresciani R AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Bosisio, Daniela AU - Bosisio D AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. FAU - Sozzani, Silvano AU - Sozzani S AD - Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Humanitas Clinical Research Center, Rozzano, Italy. Electronic address: silvano.sozzani@unibs.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160315 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (Interleukin-15) RN - 0 (Vascular Endothelial Growth Factor C) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Cell Communication MH - Cells, Cultured MH - Coculture Techniques MH - Dendritic Cells/*physiology MH - Endothelium, Lymphatic/*physiology MH - Humans MH - Inflammation/*immunology MH - Interferon-gamma/immunology MH - Interleukin-15/metabolism MH - Killer Cells, Natural/*immunology MH - *Lymphangiogenesis MH - Lymphatic Vessels/*physiology MH - Macrophages/physiology MH - Monocytes/physiology MH - Vascular Endothelial Growth Factor C/*metabolism OTO - NOTNLM OT - Angiogenesis OT - Cytokines OT - LEC OT - NK cells OT - VEGF-C EDAT- 2016/03/19 06:00 MHDA- 2017/10/17 06:00 CRDT- 2016/03/19 06:00 PHST- 2016/03/07 00:00 [received] PHST- 2016/03/11 00:00 [accepted] PHST- 2016/03/19 06:00 [entrez] PHST- 2016/03/19 06:00 [pubmed] PHST- 2017/10/17 06:00 [medline] AID - S0165-2478(16)30033-5 [pii] AID - 10.1016/j.imlet.2016.03.008 [doi] PST - ppublish SO - Immunol Lett. 2016 May;173:26-35. doi: 10.1016/j.imlet.2016.03.008. Epub 2016 Mar 15.