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Originally published online as doi:10.1189/jlb.0307164 on August 30, 2007

Published online before print August 30, 2007
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(Journal of Leukocyte Biology. 2007;82:1473-1480.)
© 2007 by Society for Leukocyte Biology

Placental growth factor down-regulates type 1 T helper immune response by modulating the function of dendritic cells

Yu-Li Lin*, Yu-Chih Liang{dagger} and Bor-Luen Chiang*,1

* Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, and Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; and
{dagger} Graduate Institute of Biomedical Technology, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China

1Correspondence: Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan, R.O.C. E-mail: gicmbor{at}ntu.edu.tw

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 I{kappa}B{alpha} phosphorylation and NF-{kappa}B activity. Taken together, our data demonstrate that the immunosuppressive properties of PlGF are through the NF-{kappa}B 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.

Key Words: T cells • Th1/Th2 cells • signal transduction




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