Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy.

During early pregnancy, decidual innate lymphoid cells (dILCs) interact with surrounding maternal cells and invading fetal extravillous trophoblasts (EVT). Here, using mass cytometry, we characterise five main dILC subsets: decidual NK cells (dNK)1-3, ILC3s and proliferating NK cells. Following stimulation, dNK2 and dNK3 produce more chemokines than dNK1 including XCL1 which can act on both maternal dendritic cells and fetal EVT. In contrast, dNK1 express receptors including Killer-cell Immunoglobulin-like Receptors (KIR), indicating they respond to HLA class I ligands on EVT. Decidual NK have distinctive organisation and content of granules compared with peripheral blood NK cells. Acquisition of KIR correlates with higher granzyme B levels and increased chemokine production in response to KIR activation, suggesting a link between increased granule content and dNK1 responsiveness. Our analysis shows that dILCs are unique and provide specialised functions dedicated to achieving placental development and successful reproduction.This work was funded by the Wellcome Trust (Grant 200841/Z/16/Z to FC and AM), the Medical Research Council (Grant MR/P001092/1 to AS), the National Institutes of Health (Grants NIH U01 AI090905 and R01 AI17892 to PP), AstraZeneca-MedImmune, the Centre For Trophoblast Research (CTR) and the Cambridge NIHR BRC Cell Phenotyping Hub to FC. OH was supported by a AstraZeneca-MedImmune-Cambridge PhD fellowship. MAI was supported by The Wenner-Gren Foundation, Stockholm, Sweden