Pregnancy-specific glycoprotein 1a activates dendritic cells to provide signals for Th17-, Th2-, and Treg-cell polarization

Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
European Journal of Immunology (Impact Factor: 4.03). 06/2012; 42(6):1573-84. DOI: 10.1002/eji.201142140
Source: PubMed


Because of their plasticity and central role in orchestrating immunity and tolerance, DCs can respond to pregnancy-specific signals, thus promoting the appropriate immune response in order to support pregnancy. Here, we show that pregnancy-specific glycoprotein (PSG1a), the major variant of PSG released into the circulation during pregnancy, targets DCs to differentiate into a subset with a unique phenotype and function. This semi-mature phenotype is able to secrete IL-6 and TGF-β. PSG1a also affected the maturation of DCs, preventing the up-regulation of some costimulatory molecules, and inducing the secretion of TGF-β or IL-10 and the expression of programmed death ligand 1 (PD-L1) in response to TLR-9 or CD40 ligation. In addition, PSG1a-treated DCs promoted the enrichment of Th2-type cytokines, IL-17-producing cells, and Treg cells from CD4(+) T cells from DO11.10 Tg mice. Moreover, in vivo expression of PSG1a promoted the expansion of Ag-specific CD4(+) CD25(+) Foxp3(+) Treg cells and IL-17-, IL-4-, IL-5-, and IL-10-secreting cells able to protect against Listeria monocytogenes infection. Taken together, our data indicate that DCs can be targeted by PSG1a to generate the signals necessary to mount an appropriate, well-balanced, and effective immune response able to protect against invading pathogens while at the same time being compatible with a successful pregnancy.

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Available from: Laura Cervi, Dec 03, 2014
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    • "PSGs isolated from the human placenta have an inhibitory effect on phytohaemagglutinin or allogeneically stimulated lymphocytes [7], [8]. Subsequently, it was shown that recombinant mouse and human PSGs induce production of anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor beta-1 (TGFβ1) by monocytic, macrophage and dendritic lineages in vitro and in vivo [9]–[14]. In the human, elevated PSG levels are associated with improved symptoms of rheumatoid arthritis during pregnancy [15]. "
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    American Journal Of Reproductive Immunology 02/2013; 69(4). DOI:10.1111/aji.12097 · 2.44 Impact Factor
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    ABSTRACT: Among several explanations for the acceptance of the fetus, the one that suggests that the maternal immune system is suppressed or modified has been the subject of many studies. Thus, it has been proposed that the cells of innate immune system might be able to distinguish the pregnant from the non-pregnant state producing a signal, the so-called signal P. We have previously proposed that pregnancy-specific glycoprotein 1a (PSG1a), a representative member of the main glycoprotein family secreted by placental trophoblast, may modulate the activation of antigen-presenting cells promoting the T-cell shift of the maternal cell immunity toward a less harmful phenotype. In this review, we summarize current knowledge concerning the contribution of pregnancy-specific glycoprotein 1a (PSG1a) to modulate the maternal innate and adaptive immune response in order to assure a successful pregnancy.
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