Placental growth factor down-regulates type 1 T helper immune response by modulating the function of dendritic cells.
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-alpha 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 IkappaBalpha phosphorylation and NF-kappaB activity. Taken together, our data demonstrate that the immunosuppressive properties of PlGF are through the NF-kappaB 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.
Lin
Yu-Li
YL
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Liang
Yu-Chih
YC
Chiang
Bor-Luen
BL
D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D045142:Cross-Priming / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000494:pharmacology*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D020672:I-kappa B Proteins; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072000:NF-KappaB Inhibitor alpha; D000072483:Placenta Growth Factor; D018664:Interleukin-12; D040281:Vascular Endothelial Growth Factor Receptor-1