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

Abstract

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.

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells

“…The leukocyte layer was collected and washed in PBS. Decidual samples and blood were processed as described previously ( Huhn et al, 2020 ).…”

Uterine Natural Killer Cell Heterogeneity: Lessons From Mouse Models

“…Single-cell RNA sequencing comparing cells isolated from first trimester decidual basalis and matched peripheral blood demonstrated three distinct NK cell subsets in decidua basalis, dNK1-3, distinct from pbNK cells (55). High dimensional CyTOF analysis found dNK1-3 mixed with populations of proliferating dNK, dILC3 and pbNK cells suggestive of mixed origins of decidual lineages (31). The dNK1 cells resembled a recently identified "pregnancy trained dNK cell" subset found in repeated pregnancy (56) similarly to expanded ILC1s of mouse second pregnancy (57).…”

“…Here, "uNK" cells will refer to NK cells in human and mouse implantation sites. Emerging evidence indicates that uNK cells are heterogeneous and contribute to pregnancy success, although they are phenotypically and functionally distinct from conventional NK cells in the circulation (28)(29)(30)(31).…”

Sharing Knowledge With Young and Established Students of Immunology by the Neapolitan Gulf at the Ruggero Ceppellini Advanced School

“…One illustrative example may be the interactions of maternal KIR on uterine NK cells with fetal HLA-C molecules on the placental cells, which may engage in a molecular conversation that, rather than leading to allorecognition-driven rejection, may in fact contribute to uterine vascular remodeling and placental growth (6). Adding to the complexity of the maternal-fetal interactions is the heterogeneity of immune cells, revealed recently by singe-cell RNA-sequencing (21) and mass cytometry (22). Mass cytometry has been applied to study also the fluctuations in blood immune cells throughout pregnancy (23,24).…”