Molecular definition of group 1 innate lymphoid cells in the mouse uterus

Iva Filipovic, Laura Chiossone, Paola Vacca, Russell S. Hamilton, Tiziano Ingegnere, Jean-Marc Doisne, Delia A. Hawkes, Maria Cristina Mingari, Andrew M. Sharkey, Lorenzo Moretta and Francesco Colucci ()
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Iva Filipovic: NIHR Cambridge Biomedical Research Centre
Laura Chiossone: G. Gaslini Institute, Genoa
Paola Vacca: Policlinico San Martino IRCCS per l’Oncologia, Genoa
Russell S. Hamilton: University of Cambridge
Tiziano Ingegnere: IRCCS Bambino Gesù Children’s Hospital
Jean-Marc Doisne: NIHR Cambridge Biomedical Research Centre
Delia A. Hawkes: NIHR Cambridge Biomedical Research Centre
Maria Cristina Mingari: Policlinico San Martino IRCCS per l’Oncologia, Genoa
Andrew M. Sharkey: University of Cambridge
Lorenzo Moretta: IRCCS Bambino Gesù Children’s Hospital
Francesco Colucci: NIHR Cambridge Biomedical Research Centre

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Determining the function of uterine lymphocytes is challenging because of the dynamic changes in response to sex hormones and, during pregnancy, to the invading foetal trophoblast cells. Here we provide a genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (ILCs) at mid-gestation. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and have gene signatures associated with TGF-β responses and interactions with trophoblast, epithelial, endothelial, smooth muscle cells, leucocytes and extracellular matrix. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. Eomes−CD49a+ ILC1s dominate before puberty, and specifically expand in second pregnancies when the expression of the memory cell marker CXCR6 is upregulated. These results identify trNK cells as the cellular hub of uterine group 1 ILCs, and mark CXCR6+ ILC1s as potential memory cells of pregnancy.

Date: 2018
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DOI: 10.1038/s41467-018-06918-3

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