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Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG 2D ligand expression in human pre‐eclamptic placenta and target it for NK cell attack
Author(s) -
Vinnars MarieTherese,
Björk Emma,
Nagaev Ivan,
Ottander Ulrika,
Bremme Katarina,
Holmlund Ulrika,
SverremarkEkström Eva,
MinchevaNilsson Lucia
Publication year - 2018
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12969
Subject(s) - nkg2d , placenta , cytokine , cytotoxic t cell , immunology , chorionic villi , inflammation , receptor , immune system , downregulation and upregulation , biology , medicine , fetus , pregnancy , in vitro , biochemistry , gene , genetics
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 NKG 2D receptor and its ligands MICA /B and ULBP 1‐3 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 NKG 2D 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 NKG 2D 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 NKG 2D receptor‐ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.