title: Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation.
abstract: Dendritic cells (DCs) are antigen (Ag)-presenting cells that activate and stimulate effective immune responses by T cells, but can also act as negative regulators of these responses and thus play important roles in immune regulation. Pro-angiogenic vascular endothelial growth factor (VEGF) has been shown to cause defective DC differentiation and maturation. Previous studies have demonstrated that the addition of VEGF to DC cultures renders these cells weak stimulators of Ag-specific T cells due to the inhibitory effects mediated by VEGF receptor 1 (VEGFR1) and/or VEGFR2 signalling. As the enzyme indoleamine 2,3-dioxygenase (IDO) is recognised as an important negative regulator of immune responses, this study aimed to investigate whether VEGF affects the expression of IDO by DCs and whether VEGF-matured DCs acquire a suppressor phenotype. Our results are the first to demonstrate that VEGF increases the expression and activity of IDO in DCs, which has a suppressive effect on Ag-specific and mitogen-stimulated lymphocyte proliferation. These mechanisms have broad implications for the study of immunological responses and tolerance under conditions as diverse as cancer, graft rejection and autoimmunity.
authors.affiliation: Centro de Pesquisa Experimental, Instituto Israelita de Ensino e Pesquisa Albert Einstein.
authors.forename: Luciana Cavalheiro
authors.initials: LC
authors.lastname: Marti
authors.affiliation: Centro de Pesquisa Experimental, Instituto Israelita de Ensino e Pesquisa Albert Einstein.
authors.forename: Lorena
authors.initials: L
authors.lastname: Pavon
authors.affiliation: Centro de Pesquisa Experimental, Instituto Israelita de Ensino e Pesquisa Albert Einstein.
authors.forename: Patricia
authors.initials: P
authors.lastname: Severino
authors.affiliation: Centro de Pesquisa Experimental, Instituto do Cérebro, Hospital Israelita Albert Einstein, São PauloSP, Brasil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sibov
authors.affiliation: Centro de Pesquisa Experimental, Instituto Israelita de Ensino e Pesquisa Albert Einstein.
authors.forename: Daiane
authors.initials: D
authors.lastname: Guilhen
authors.affiliation: Centro de Pesquisa Experimental, Instituto Israelita de Ensino e Pesquisa Albert Einstein.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Moreira-Filho
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis; D017209:Apoptosis; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000648:ultrastructure; D009336:Necrosis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D000954:Antigens, Surface; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D042461:Vascular Endothelial Growth Factor A