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dc.contributor.authorFilipovic, Iva
dc.contributor.authorChiossone, Laura
dc.contributor.authorVacca, Paola
dc.contributor.authorHamilton, Russell
dc.contributor.authorIngegnere, Tiziano
dc.contributor.authorDoisne, Jean-Marc
dc.contributor.authorHawkes, Delia
dc.contributor.authorMingari, Maria Cristina
dc.contributor.authorSharkey, Andrew
dc.contributor.authorMoretta, Lorenzo
dc.contributor.authorColucci, Francesco
dc.description.abstractDetermining the function of uterine lymphocytes is challenging because of the rapidly changing nature of the organ in response to sex hormones and, during pregnancy, to the invading fetal trophoblast cells. Here we provide the first genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (g1 ILCs) at mid-gestation. The composition of g1 ILCs fluctuates throughout reproductive life, with Eomes-veCD49a+ ILC1s dominating before puberty and specifically expanding in second pregnancies, when the expression of CXCR6, a marker of memory cells, is upregulated. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and showcase gene signatures of responsiveness to TGF-β, connections with trophoblast, epithelial, endothelial and smooth muscle cells, leucocytes, as well as extracellular matrix. Unexpectedly, trNK cells express genes involved in anaerobic glycolysis, lipid metabolism, iron transport, protein ubiquitination, and recognition of microbial molecular patterns. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. These results identify trNK cells as the cellular hub of uterine g1 ILCs at mid-gestation and mark CXCR6+ ILC1s as potential memory cells of pregnancy.
dc.description.sponsorshipThis work was funded by a Wellcome Trust Investigator Award 200841/Z/16/Z, the Centre for Trophoblast Research (CTR), and the Cambridge NIHR BRC Cell Phenotyping Hub to FC, the Associazione Italiana Ricerca per la Ricerca sul Cancro (AIRC) - Special Project 5x1000 no. 9962, AIRC IG 2017 Id.19920 and AIRC 2014 Id. 15283 to LM, and Ministero della Salute RF-2013, GR-2013-02356568 to PV. IF was funded by a CTR PhD fellowship.
dc.publisherSpringer Nature
dc.rightsAttribution 4.0 International
dc.titleMolecular definition of group 1 innate lymphoid cells in the mouse uterus
prism.publicationNameNature Communications
dc.contributor.orcidFilipovic, Iva [0000-0002-8166-5500]
dc.contributor.orcidHamilton, Russell [0000-0002-0598-3793]
dc.contributor.orcidSharkey, Andrew [0000-0002-5072-7748]
dc.contributor.orcidColucci, Francesco [0000-0001-5193-6376]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (200841/Z/16/Z)
pubs.funder-project-idMedical Research Council (MR/P001092/1)

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International