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Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
Department of Clinical Microbiology, County Hospital Ryhov, Jönköping, Sweden.
Mucosal Immunity, Helmholtz Centre for Infection Research (HCI), Braunschweig, Germany.
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2008 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 3, no 4, e2078- p.Article in journal (Refereed) Published
Abstract [en]

Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known.

Methodology/Principal Findings: 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.

Conclusions/Significance: 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.

Place, publisher, year, edition, pages
2008. Vol. 3, no 4, e2078- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-14686DOI: 10.1371/journal.pone.0002078OAI: diva2:24260
Original Publication: Charlotte Gustafsson (Lidström), Jenny Mjösberg, Andreas Matussek, Robert Geffers, Leif Matthiesen, Göran Berg, Surendra Sharma, Jan Buer and Jan Ernerudh, Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype, 2008, PLoS ONE, (3), 4, e2078. Copyright: Public Library of Science (PLoS) Available from: 2007-10-10 Created: 2007-10-10 Last updated: 2010-03-19
In thesis
1. Local Immune regulation in human pregnancy: with focus on decidual macrophages
Open this publication in new window or tab >>Local Immune regulation in human pregnancy: with focus on decidual macrophages
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During pregnancy, the woman carries a fetus partly foreign to her immune system, because of the expression of paternal antigens. Despite this, the fetus is normally tolerated and not rejected, as is often the case with organs in allogeneic transplantations. Systemic changes in maternal blood occur during pregnancy but, perhaps of greater importance, are changes in tissues locally in the uterus. The pregnant uterine endometrium, the decidua, is infiltrated by large numbers of leukocytes, mainly natural killer (NK) cells but also macrophages and T lymphocytes. Further, various cytokines are known to be secreted at the fetomaternal interface. However, the functions of these cells and the cytokine networks are not fully understood. The aim of this thesis was to investigate the local immune balance in normal human pregnancy decidua, both in the early phase of pregnancy and at parturition.

First trimester decidual mononuclear cells, NK cells and macrophages were all shown to secrete IFN-γ, IL-4 and IL-10, as detected by ELISPOT. The secretion was not mirrored in blood from the same subjects. A significantly larger number of decidual macrophages secreted IL-10 than did their blood counterparts, indicating potential regulatory functions of this cell type.

Further examination of early pregnancy decidual macrophages by microarray revealed 120 genes being differentially regulated at the transcriptional level in decidual compared to blood monocytes/macrophages. Several genes were associated with alternative activation/M2 polarization of macrophages, including CCL-18, CD209, IGF-1, MRC-1 and FN-1. Genes connected to immune regulation and tissue remodelling were common, in line with the potential functions for this cell type in utero. In addition, some molecules not previously connected to decidual macrophages, such as TREM-2, A2M and PGDS, were found to be upregulated, gaining new insights into the regulatory functions of decidual macrophages.

Term decidual mononuclear cells spontaneously secrete IFN-γ, TNF, IL-4, IL-10, and TGF-β. No differences were seen between tissues obtained before and after the onset of labour, indicating that decidual mononuclear cells are not the main cell population responsible for plausible cytokine regulation in the process of labour induction. Placental and fetal membranes as well as cells in the maternal systemic circulation may instead contribute to a possible shift in immune balance prior to pregnancy termination.

In conclusion, decidual leukocytes, including NK cells and macrophages, are potential producers of both Th1-like/pro-inflammatory and Th2-like/anti-inflammatory cytokines in early pregnancy as well as at parturition. Decidual macrophages are of a specialized phenotype with effector functions contributing to a proper invasion of the placenta and to immunological protection of the semi-allogeneic fetus. This thesis adds new knowledge on local immune balance during normal human pregnancy, however, the clinical significance of the presented data needs to be clarified.

Place, publisher, year, edition, pages
Institutionen för klinisk och experimentell medicin, 2007. 68 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1016
reproduction, placenta, leukocyte, ELISPOT
National Category
Immunology in the medical area
urn:nbn:se:liu:diva-9985 (URN)978-91-85895-85-4 (ISBN)
Public defence
2007-10-19, Berzeliussalen, Hälsouniversitetet, Universitetssjukhuset, Linköping, 09:00 (English)
Available from: 2007-10-10 Created: 2007-10-10 Last updated: 2013-08-29

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