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Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood: Implications for suppressor macrophages in decidua
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
Department of Pediatrics & Department of Pathology, Brown University and Women and Infants' Hospital of Rhode Island, Providence, RI, USA.
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2003 (English)In: American Journal of reproductive immunology, ISSN 8755-8920, Vol. 50, no 6, 444-452 p.Article in journal (Refereed) Published
Abstract [en]

Problem: Local immune modulation has been shown to be of considerable importance for the maintenance of successful pregnancy. We have previously reported the secretion of interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-10 in human decidua from early normal pregnancy. The aim of this study was to investigate the cellular source of cytokine secretion in the decidua, and compare this to secretion patterns in peripheral blood.

Method of study: Decidual tissue and peripheral blood was collected from 20 women undergoing surgical abortion during first trimester pregnancy. Monocytes/macrophages and NK cells were enriched by immunomagnetic cell separation and cytokine secretion was detected by enzyme-linked immunosorbent spot-forming cell assay.

Results: Decidual and peripheral monocytes/macrophages and NK cells spontaneously secrete IFN-γ, IL-4 and IL-10. The number of IL-10 secreting cells was significantly higher in decidual macrophages compared with decidual non-monocytic cells as well as compared with blood monocytes/macrophages. These differences were not seen for IFN-γ or IL-4.

Conclusions: Our results indicate that decidual macrophages subserve important suppressive functions in the pregnant uterus.

Place, publisher, year, edition, pages
2003. Vol. 50, no 6, 444-452 p.
Keyword [en]
Decidua, IFN-γ, IL-10, IL-4, macrophages, natural killer cells, pregnancy
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14685DOI: 10.1046/j.8755-8920.2003.00112.xOAI: oai:DiVA.org:liu-14685DiVA: diva2:24259
Available from: 2007-10-10 Created: 2007-10-10 Last updated: 2013-08-29
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.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1016
Keyword
reproduction, placenta, leukocyte, ELISPOT
National Category
Immunology in the medical area
Identifiers
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)
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Available from: 2007-10-10 Created: 2007-10-10 Last updated: 2013-08-29

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Lidström Gustafsson, CharlotteMatthiesen, LeifBerg, GöranErnerudh, JanEkerfelt, Christina

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Lidström Gustafsson, CharlotteMatthiesen, LeifBerg, GöranErnerudh, JanEkerfelt, Christina
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Clinical Immunology Faculty of Health SciencesDepartment of Clinical Immunology and Transfusion MedicineObstetrics and gynecology Department of Gynecology and Obstetrics in LinköpingDepartment of Clinical and Experimental Medicine
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