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Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
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2018 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 80, no 1, article id e12969Article in journal (Refereed) Published
Abstract [en]

Problem: Pre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1-3 in PE- and normal placenta.

Method of study: The cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1-3 in PE placenta were assessed and compared to those in normal placenta using real-time quantitative RT-PCR.

Results: The cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta.

Conclusion: The destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor-ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018. Vol. 80, no 1, article id e12969
Keywords [en]
cytokines, inflammation, natural killer cells, NKG2D receptor-ligand system, pre-eclampsia, Treg
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-150750DOI: 10.1111/aji.12969ISI: 000436401600013PubMedID: 29741244Scopus ID: 2-s2.0-85046661409OAI: oai:DiVA.org:umu-150750DiVA, id: diva2:1239434
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved

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Vinnars, Marie-ThereseBjörk, EmmaNagaev, IvanOttander, UlrikaMincheva-Nilsson, Lucia

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Vinnars, Marie-ThereseBjörk, EmmaNagaev, IvanOttander, UlrikaSverremark-Ekström, EvaMincheva-Nilsson, Lucia
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Department of Clinical MicrobiologyClinical ImmunologyObstetrics and Gynecology
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American Journal of Reproductive Immunology
Immunology in the medical area

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