Interleukin‐15 contributes to decidual natural killer cell loss via interferon‐γ during early pregnancy in the pre‐eclamptic BPH/5 mouse model (1083.1)

Abstract

During early pregnancy dNK cells promote decidualization, which is critical for uterine angiogenesis and placentation. IL‐15 activates dNK cells, which release IFN‐γ to orchestrate vessel remodeling for proper placental perfusion. However, high levels of IFN‐ γ induce apoptosis of dNK cells at the maternal‐fetal interface. Reduced perfusion of the fetoplacental unit is a hallmark of PE. Our previous studies showed that BPH/5 mice, a rodent model of spontaneous PE, have increased peripheral inflammation. We hypothesize that peripheral inflammation in early pregnancy contributes to elevated IL‐15, which results in dNK cell apoptosis. Virgin BPH/5 mice had significantly elevated uterine IL‐15 mRNA as compared to C57 controls. Other pro‐inflammatory cytokines were unchanged. At e4.5 and e5.5, when decidualization first begins, we observed significantly increased IL‐15 mRNA in BPH/5 implantation sites compared to controls (60‐fold, 20‐fold respectively, p<0.05, n=4). Further, BPH/5 dNK cell mRNA expression was similar to controls at e4.5 but dramatically reduced at e5.5 (10‐fold, p<0.05, n=4). This finding was confirmed by flow cytometry (BPH/5 0.7 x 103 cells vs C57 9.7 x 103 cells, p<0.05, n=4), and was attributed to a 3‐fold increase in IFN‐γ mRNA. These findings support the hypothesis that early pregnancy events may lead to impaired uterine angiogenesis which precedes the development of PE in this model.Grant Funding Source: #12POST11250010; HL63887, HL84207, 12SDG9160010