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.
Highlights
During early pregnancy, decidual innate lymphoid cells interact with surrounding maternal cells and invading fetal extravillous trophoblasts (EVT)
We set out to characterise the heterogeneity of matched cryopreserved first trimester decidual mononuclear cells and Peripheral blood mononuclear cells (PBMCs) using a 41-marker mass cytometry panel (Fig. 1a and Supplementary Table 1)
As this is the first study of decidual mononuclear cells (dMCs) using mass cytometry, we compared a subset of our panel of antibodies with results generated by conventional flow cytometry
Summary
Decidual innate lymphoid cells (dILCs) interact with surrounding maternal cells and invading fetal extravillous trophoblasts (EVT). Decidual NK have distinctive organisation and content of granules compared with peripheral blood NK cells. PbNK from patients with Chediak-Higashi syndrome (CHS) possess NK cells with fewer, larger granules that do not polarise towards canonical NK cell target cells compared to normal pbNK25,26 Their cytokine production is more efficient[27]. We demonstrate that KIR acquisition by dNK is associated with increased granule content at steady state and increased functionality upon cross-linking of an activating KIR. This comprehensive analysis of the phenotype and functional characteristics of dILCs reveals their unique features in this decidual environment dedicated to successful reproduction
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
