Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype

Division of Clinical Immunology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(4):e2078. DOI: 10.1371/journal.pone.0002078
Source: PubMed

ABSTRACT Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known.
Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications.
The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.

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Available from: Andreas Matussek, Sep 28, 2015
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    • "Indeed, co-culture of uNK cells and EVT isolated from the same patient decreases secretion of Ang-1, VEGF-C, IL-6, IL-8, and TGF-␤1, irrespective of gestational age (Lash et al., 2011). Decidual macrophages have also been proposed to play a role in regulating EVT invasion, although studies with isolated decidual macrophages have been limited and results have been extrapolated from the use of peripheral blood macrophages, which may differ phenotypically (Gustafsson et al., 2008). Renaud et al. (2005) demonstrated that peripheral blood macrophages activated with lipopolysaccharide inhibit the invasion of the trophoblast cell line HTR-8/SVneo, via TNF-␣ and increased PAI-1. "
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    ABSTRACT: Invasion of extravillous trophoblast cells (EVT) into the maternal tissues is a key step in the development of a successful pregnancy, excessive and insufficient EVT invasion being associated with pregnancy complications. These pregnancy complications include preeclampsia and fetal growth restriction, both of which are associated with maternal and fetal morbidity and mortality at the time of birth and with increased risk of cardiovascular disease, diabetes and obesity in adult life for infants born from these conditions. In addition, women who develop preeclampsia are also at a greater risk of cardiovascular disease in later life. Many factors, protein and environmental, have been shown to both up- and down-regulate this process in vitro via different mechanisms. The redundancy observed in the regulation of this system suggests that dysregulation of one factor may not contribute to the pathological conditions of EVT invasion and that the relative local concentrations of many different factors may be more important. This review article explores the possibility that the modulation of EVT invasion as a therapeutic target for pregnancies affected by preeclampsia and fetal growth restriction may not be possible or needs to concentrate on the modulation of cell activity as a whole and not of one particular factor.
    Journal of Reproductive Immunology 10/2014; 104-105. DOI:10.1016/j.jri.2014.04.002 · 2.82 Impact Factor
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    • "Macrophages bearing a predominant alternative activation profile are involved in the human placentation process and the transition of the pro-inflammatory response characteristic of implantation to an immunosuppressive profile in the second trimester [32], [34], [35]. In this study, we demonstrated that CD16 which represent a monocyte subpopulation with a unique functional role to regulate inflammation [34], [36] was up-regulated. "
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    ABSTRACT: Macrophages at the maternal-placental interface coordinate opposite demands under the control of trophoblast cells such as the response against pathogens on one hand, and apoptotic cell clearance and wound healing with the production of suppressor cytokines. Here, we investigated whether trophoblast cells induce maternal monocyte activation towards an alternative activated macrophage profile and whether bacterial or viral stimuli modulate their migratory properties. We used an in vitro model of the maternal-placental interface represented by co-cultures of CD14+ cells isolated from fertile women with first trimester trophoblast cell line (Swan-71 cells) in the presence or absence of pathogen associated molecular pattern (PAMP) stimuli lipopolysaccharide (LPS), peptidoglycan (PGN) or poly [I:C]). Maternal CD14+ cells showed increased CD16 and CD39 expression, both markers associated to an alternative activation profile, with no changes in CD80 expression after trophoblast cell interaction. These changes were accompanied by increased IL-10 and decreased IL-12 production by CD14+ cells. After stimulation with LPS, PGN or poly [I:C], monocytes co-cultured with trophoblast cells had lower production of TNF-α and IL-1β compared with non co-cultured monocytes. Interestingly, monocyte migration towards trophoblast cells was prevented in the presence of LPS or PGN but not after 24h of stimulation with poly [I:C]. LPS or PGN also decreased CCR5, CXCL-8 and CCL5 expression. Finally, trophoblast cells co-cultured with monocytes in the presence of pathological stimuli failed to increase chemokine expression, indicating a bidirectional effect. In conclusion, trophoblast might 'instruct' maternal monocytes to express an alternative activation profile and restrain their early recruitment under pathological threats as one of the first strategies to avoid potential tissue damage at the maternal-placental interface.
    PLoS ONE 05/2014; 9(5):e97147. DOI:10.1371/journal.pone.0097147 · 3.23 Impact Factor
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    • "A more recent study examined dMac in the first trimester using gene micro-array analysis. The authors found that compared to peripheral blood macrophages, dMacs have a gene expression profile, which biases toward alternatively activated macrophages or M2 phenotype, which suggests that dMacs are likely immunosuppressive (29). "
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    ABSTRACT: Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface - the decidua, the site of implantation, and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, pre-eclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages) make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3(+) regulatory T cells are crucial for ensuring immune tolerance toward the semi-allogeneic fetus. Additionally, another population of CD4(+)HLA-G(+) suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy.
    Frontiers in Immunology 03/2014; 5:125. DOI:10.3389/fimmu.2014.00125
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