First trimester human decidua is composed of decidual cells, CD56brightCD16-decidual natural killer (dNK) cells, and macrophages. Decidual cells incubated with NK cell-derived IFN-γ and either macrophage-derived TNF-α or IL-1β synergistically enhanced mRNA and protein expression of IP-10 and I-TAC. Both chemokines recruit CXCR3-expressing NK cells. This synergy required IFN-γ receptor 1 and 2 mediation via JAK/STAT and NFκB signaling pathways. However, synergy was not observed on neutrophil, monocyte, and NK cell-recruiting chemokines. Immunostaining of first trimester decidua localized IP-10, I-TAC, IFN-γR1, and -R2 to vimentin-positive decidual cells versus cytokeratin-positive interstitial trophoblasts. Flow cytometry identified high CXCR3 levels on dNK cells and minority peripheral CD56brightCD16-pNK cells and intermediate CXCR3 levels on the majority of CD56dimCD16+pNK cells. Incubation of pNK cells with either IP-10 or I-TAC elicited concentration-dependent enhanced CXCR3 levels and migration of both pNK cell subsets that peaked at 10 ng/mL, whereas each chemokine at a concentration of 50 ng/mL inhibited CXCR3 expression and pNK cell migration. Deciduae from women with preeclampsia, a leading cause of maternal and fetal morbidity and mortality, displayed significantly lower dNK cell numbers and higher IP-10 and I-TAC levels versus gestational age-matched controls. Significantly elevated IP-10 levels in first trimester sera from women eventually developing preeclampsia compared with controls, identifying IP-10 as a novel, robust early predictor of preeclampsia.

adult, article, cell migration, clinical article, controlled study, decidua, female, first trimester pregnancy, human, human cell, human tissue, macrophage, natural killer cell, pathogenesis, prediction, preeclampsia, priority journal, protein expression, protein localization
dx.doi.org/10.1016/j.ajpath.2013.05.029, hdl.handle.net/1765/41479
American Journal of Pathology
Erasmus MC: University Medical Center Rotterdam

Lockwood, C.J, Huang, S.J, Chen, C.P, Xu, J, Faramarzi, S, Kayisli, O, … Schatz, F. (2013). Decidual cell regulation of natural killer cell-recruiting chemokines: Implications for the pathogenesis and prediction of preeclampsia. American Journal of Pathology, 183(3), 841–856. doi:10.1016/j.ajpath.2013.05.029