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

Author

Listed:
  • Oisín Huhn

    (National Institute for Health Research Cambridge Biomedical Research Centre
    University of Cambridge
    Oncology R&D
    University of Cambridge)

  • Martin A. Ivarsson

    (University of Cambridge
    Karolinska University Hospital)

  • Lucy Gardner

    (University of Cambridge)

  • Mike Hollinshead

    (University of Cambridge)

  • Jane C Stinchcombe

    (University of Cambridge)

  • Puran Chen

    (Karolinska University Hospital)

  • Norman Shreeve

    (National Institute for Health Research Cambridge Biomedical Research Centre
    University of Cambridge)

  • Olympe Chazara

    (University of Cambridge
    University of Cambridge
    Biopharmaceuticals R&D, AstraZeneca)

  • Lydia E. Farrell

    (University of Cambridge
    University of Cambridge)

  • Jakob Theorell

    (University of Oxford
    Karolinska Institutet)

  • Hormas Ghadially

    (Oncology R&D)

  • Peter Parham

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Gillian Griffiths

    (University of Cambridge)

  • Amir Horowitz

    (Tisch Cancer Institute Icahn School of Medicine at Mount Sinai)

  • Ashley Moffett

    (University of Cambridge
    University of Cambridge)

  • Andrew M. Sharkey

    (University of Cambridge
    University of Cambridge)

  • Francesco Colucci

    (National Institute for Health Research Cambridge Biomedical Research Centre
    University of Cambridge)

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.

Suggested Citation

  • 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 Par, 2020. "Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14123-z
    DOI: 10.1038/s41467-019-14123-z
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    Cited by:

    1. Jake R. Thomas & Anna Appios & Emily F. Calderbank & Nagisa Yoshida & Xiaohui Zhao & Russell S. Hamilton & Ashley Moffett & Andrew Sharkey & Elisa Laurenti & Courtney W. Hanna & Naomi McGovern, 2023. "Primitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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