title: Dendritic cell-derived VEGF-A plays a role in inflammatory angiogenesis of human secondary lymphoid organs and is driven by the coordinated activation of multiple transcription factors.
abstract: Lymph node expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Previous work in mice has shown that this process depends on the presence of VEGF-A produced by B cells, macrophages and stromal cells. In humans, however, the cell types and the mechanisms regulating the intranodal production of VEGF-A remain elusive. Here we show that CD11c+ cells represent the main VEGF-A-producing cell population in human reactive secondary lymphoid organs. In addition we find that three transcription factors, namely CREB, HIF-1α and STAT3, regulate the expression of VEGF-A in inflamed DCs. Both HIF-1α and STAT3 are activated by inflammatory agonists. Conversely, CREB phosphorylation represents the critical contribution of endogenous or exogenous PGE2. Taken together, these results propose a crucial role for DCs in lymph node inflammatory angiogenesis and identify novel potential cellular and molecular targets to limit inflammation in chronic diseases and tumors.
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: William
authors.initials: W
authors.lastname: Vermi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Gianello
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonardi
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 Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Naldini
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.|Humanitas Clinical and Research Centre, Rozzano, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bosisio
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D047468:Immunoprecipitation; D007249:Inflammation; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology; D022423:Myeloid Cells / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D039521:CD11c Antigen; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008024:Ligands; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: CD1a+ interdigitating DCs; CD1c+ DCs; DAMPs; PAMPs; Pathology Section; draining lymph node