liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Cytokine secretion in decidual mononuclear cells from term human pregnancy with or without labour: ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha
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.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
Show others and affiliations
2006 (English)In: Journal of reproductive immunology, ISSN 0165-0378, Vol. 71, no 1, 41-56 p.Article in journal (Refereed) Published
Abstract [en]

Cytokines are believed to be important in maintaining pregnancy and in the process of labour induction in humans. The aim of this study was to investigate the secretion of the cytokines interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-10, transforming growth factor-β (TGF-β) and tumour necrosis factor-α (TNF-α) in decidual tissue with or without labour.

Decidual tissue was collected from 32 healthy women undergoing elective caesarean sections before the onset of labour (n = 17) or after normal vaginal delivery (n = 15). Mononuclear cells were analysed for cytokine secretion with ELISPOT. To validate the widely used method of tissue collected at caesarean sections and after vaginal deliveries as a representative of before and after labour, respectively, placenta biopsies were collected from 12 healthy women to study the expression of the prostaglandin pathway enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase (mPGES).

Decidual mononuclear cells from term human pregnancy spontaneously secrete IFN-γ, IL-4, IL-10, TGF-β and TNF-α. No difference was seen in cytokine secretion with or without labour, indicating that decidual leukocytes are not the main cell population responsible for plausible cytokine regulation in the process of termination of pregnancy. Placental tissues obtained after vaginal delivery showed a higher mRNA expression of the prostaglandin regulating molecules COX-2 and mPGES than tissues from caesarean sections before the onset of labour, validating that the model can be used as a representative of the state before and after labour.

Place, publisher, year, edition, pages
2006. Vol. 71, no 1, 41-56 p.
Keyword [en]
Parturition; Prostaglandins; COX-2; mPGES
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14687DOI: 10.1016/j.jri.2005.12.009OAI: oai:DiVA.org:liu-14687DiVA: diva2:24261
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)
Opponent
Supervisors
Available from: 2007-10-10 Created: 2007-10-10 Last updated: 2013-08-29

Open Access in DiVA

No full text

Other links

Publisher's full textLink to Ph.D. thesis

Authority records BETA

Gustafsson (Lidström), CharlotteMatthiesen, LeifBerg, GöranEkerfelt, ChristinaErnerudh, Jan

Search in DiVA

By author/editor
Gustafsson (Lidström), CharlotteMatthiesen, LeifBerg, GöranEkerfelt, ChristinaErnerudh, Jan
By organisation
Clinical Immunology Faculty of Health SciencesObstetrics and gynecology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 166 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf