Unique role of immune cells in pregnancy
Pregnancy in vertebrates is characterised by co-existence of two genetically distinct organisms with placental cells invading maternal tissues and vasculature. Uterus is very rich in NK cells, but these uterine NK cells (uNK) surprisingly are not very good killers. In the EU-funded NK IN PREGNANCY (Impact of natural killer cells on fetal and placental development) project scientists studied the role of uNK cells at the maternal-foetal tissue interface and how they impact placental and foetal development. In the first stage of the project, researchers identified NK and other innate lymphoid cells (ILCs) subsets in uterus during pregnancy using mouse model. They found that the so called tissue resident NK cells (trNK) are predominant within the uterine wall while the conventional NK cells (cNK) increased in the highly vascularised uterine mucosa (decidua). The decidua, however, did not have such subtypes of ILCs as ILC2 and ILC3. Curiously, Nuclear factor, interleukin-3 (NFIL3), a key transcription factor for all murine ILCs, was not required for trNK, ILC1 and ILC3 development. Interferon gamma (IFNg) produced by uNK cells plays an essential role in uterine spiral artery remodelling, which ensures optimal supply of oxygen and nutrients to the foetus. Deficient remodelling is associated with pregnancy complications, including pre-eclampsia, recurrent miscarriage and foetal growth deficiency. Analysis of the cytokine profiles of ILCs and uNK cell subsets demonstrated that ILC1, trNK cells and cNK cells are producers of IFNg. In conclusion, these studies characterised for the first time the role of cNK, trNK and other sub-types of ILCs in pregnancy in a mouse model. These findings support research in a rapidly evolving field and bring insights with translational applications to humans in treating pregnancy disorders.
