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

Oisín Huhn, Martin A. Ivarsson, Lucy Gardner, Mike Hollinshead, Jane C. Stinchcombe, Puran Chen, Norman Shreeve, Olympe Chazara, Lydia E. Farrell, Jakob Theorell, Hormas Ghadially, Peter Parham, Gillian Griffiths, Amir Horowitz, Ashley Moffett, Andrew M. Sharkey, Francesco Colucci

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

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.

Original languageEnglish
Article number381
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - 1 Dec 2020

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