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Placental growth factor down‐regulates type 1 T helper immune response by modulating the function of dendritic cells
Author(s) -
Lin YuLi,
Liang YuChih,
Chiang BorLuen
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0307164
Subject(s) - placental growth factor , biology , cd80 , cd14 , cd86 , cancer research , microbiology and biotechnology , cd40 , immunology , immune system , t cell , endocrinology , medicine , vascular endothelial growth factor , cytotoxic t cell , in vitro , biochemistry , vegf receptors
Placental growth factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family and represents a key regulator of angiogenic events in development and pathologic conditions. In this study, PlGF‐modulated differentiation and maturation of human dendritic cells (DCs) from CD14+ monocytes were investigated. The DC, differentiated from CD14+ monocytes in the presence of PlGF during 5 days, was referred to as “PlGF‐DC”, in contrast to the “classical‐DC”, obtained in the absence of PlGF. Treatment of PlGF‐DC or classical‐DC with PlGF resulted in the down‐regulation of CD80, CD86, CD83, CD40, and HLA‐DR expression, and CD1a was increased, as well as the inhibition of IL‐12 p70, p40, IL‐8, and TNF‐α production in response to LPS stimulation. This PlGF‐induced DC dysfunction was recovered by anti‐human VEGF receptor 1 mAb. In addition, treatment of PlGF‐DC or classical‐DC with PlGF resulted in the suppression of naïve CD4+ T cell proliferation in an allogenic MLR but up‐regulated the IL‐5 and IL‐13 secretion of the CD4+ T cell. PlGF was also able to inhibit LPS‐induced IκBα phosphorylation and NF‐κB activity. Taken together, our data demonstrate that the immunosuppressive properties of PlGF are through the NF‐κB signaling pathway. PlGF might play a major role in the pathogenesis of tumors and act as an effector molecule to skew T cell response to the Th2 phenotype, which might be more beneficial for pregnancy.