Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation

Memórias do Instituto Oswaldo Cruz

Luciana Cavalheiro Marti¹  Lorena Pavon¹  Patricia Severino¹  Tatiana Sibov¹  Daiane Guilhen¹  Carlos Alberto Moreira-filho¹ 

关键词: indoleamine-pyrrole 2;    3-dioxygenase;    dendritic cell;    vascular endothelial growth factor A;    tolerance;    immune;    lymphocytes;   

DOI  :  10.1590/0074-0276130252

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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