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dc.contributor.authorFilipovic, Ivaen
dc.contributor.authorChiossone, Lauraen
dc.contributor.authorVacca, Paolaen
dc.contributor.authorHamilton, Russellen
dc.contributor.authorIngegnere, Tizianoen
dc.contributor.authorDoisne, Jean-Marcen
dc.contributor.authorHawkes, Deliaen
dc.contributor.authorMingari, Maria Cristinaen
dc.contributor.authorSharkey, Andrewen
dc.contributor.authorMoretta, Lorenzoen
dc.contributor.authorColucci, Francescoen
dc.date.accessioned2019-01-31T09:37:14Z
dc.date.available2019-01-31T09:37:14Z
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/288605
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.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleMolecular definition of group 1 innate lymphoid cells in the mouse uterusen
dc.typeArticle
prism.number4492en
prism.publicationNameNature Communicationsen
prism.volume9en
dc.identifier.doi10.17863/CAM.35888
dcterms.dateAccepted2018-09-26en
rioxxterms.versionofrecord10.1038/s41467-018-06918-3en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-09-26en
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/Reviewen
pubs.funder-project-idWellcome Trust (200841/Z/16/Z)
pubs.funder-project-idMRC (MR/P001092/1)
cam.issuedOnline2018-10-29en


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