{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:02:13Z","timestamp":1791345733232,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["SFB F70"],"award-info":[{"award-number":["SFB F70"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["subproject F7003"],"award-info":[{"award-number":["subproject F7003"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["813343"],"award-info":[{"award-number":["813343"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PG388232"],"award-info":[{"award-number":["PG388232"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["5x1000 Program 21147"],"award-info":[{"award-number":["5x1000 Program 21147"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["MFAG\u2010Program 21311"],"award-info":[{"award-number":["MFAG\u2010Program 21311"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Type 1 innate lymphoid cells (ILC1) are tissue\u2010resident lymphocytes that provide early protection against bacterial and viral infections. Discrete transcriptional states of ILC1 have been identified in homeostatic and pathological contexts. However, whether these states delineate ILC1 with different functional properties is not completely understood. Here, we show that liver ILC1 are heterogeneous for the expression of distinct effector molecules and surface receptors, including granzyme A (GzmA) and CD160, in mice. ILC1 expressing high levels of GzmA are enriched in the liver of adult mice, and represent the main hepatic ILC1 population at birth. However, the heterogeneity of GzmA and CD160 expression in hepatic ILC1 begins perinatally and increases with age. GzmA\n                    <jats:sup>+<\/jats:sup>\n                    ILC1 differ from NK cells for the limited homeostatic requirements of JAK\/STAT signals and the transcription factor\n                    <jats:italic>Nfil3<\/jats:italic>\n                    . Moreover, by employing\n                    <jats:italic>Rorc(\u03b3t)<\/jats:italic>\n                    \u2010fate map (fm) reporter mice, we established that ILC3\u2010ILC1 plasticity contributes to delineate the heterogeneity of liver ILC1, with ROR\u03b3t\u2010fm\n                    <jats:sup>+<\/jats:sup>\n                    cells skewed toward a GzmA\n                    <jats:sup>\u2013<\/jats:sup>\n                    CD160\n                    <jats:sup>+<\/jats:sup>\n                    phenotype. Finally, we showed that ILC1 defined by the expression of GzmA and CD160 are characterized by graded cytotoxic potential and ability to produce IFN\u2010\u03b3. In conclusion, our findings help deconvoluting ILC1 heterogeneity and provide evidence for functional diversification of liver ILC1.\n                  <\/jats:p>","DOI":"10.1002\/eji.202149209","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T09:01:45Z","timestamp":1628067705000},"page":"2568-2575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Granzyme A and CD160 expression delineates ILC1 with graded functions in the mouse liver"],"prefix":"10.1002","volume":"51","author":[{"given":"Chiara","family":"Di Censo","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Marotel","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Cancer Therapeutics Program  Ottawa Ontario Canada"},{"name":"Centre for Infection, Immunity and Inflammation University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology, and Immunology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Mattiola","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity Department of Microbiology Infectious Diseases and Immunology Campus Benjamin Franklin Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Berlin Institute of Health (BIH) Anna\u2010Louisa\u2010Karsch Strasse 2  Berlin Germany"},{"name":"Deutsches Rheuma\u2010Forschungszentrum Mucosal and Developmental Immunology  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Department of Internal Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Scarno","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Peruzzi","sequence":"additional","affiliation":[{"name":"Center for Life Nano\u2010 &amp; Neuro\u2010Science Fondazione Istituto Italiano di Tecnologia  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Laffranchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julija","family":"Mazej","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Shaad","family":"Hasim","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Cancer Therapeutics Program  Ottawa Ontario Canada"},{"name":"Centre for Infection, Immunity and Inflammation University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology, and Immunology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Asif","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Cancer Therapeutics Program  Ottawa Ontario Canada"},{"name":"Centre for Infection, Immunity and Inflammation University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology, and Immunology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Tomaipitinca","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Stabile","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre for Infection, Immunity and Inflammation University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology, and Immunology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Vian","sequence":"additional","affiliation":[{"name":"Translational Immunology Section Office of Science and Technology National Institute of Arthritis Musculoskeletal and Skin Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9084-6736","authenticated-orcid":false,"given":"Massimo","family":"Gadina","sequence":"additional","affiliation":[{"name":"Translational Immunology Section Office of Science and Technology National Institute of Arthritis Musculoskeletal and Skin Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Gismondi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Yu","family":"Shih","sequence":"additional","affiliation":[{"name":"Neuro\u2010Immune Regulome Unit National Eye Institute and National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Mikami","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Capuano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bonelli","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Department of Internal Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Sozzani","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"},{"name":"IRCCS Neuromed  Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9176-9530","authenticated-orcid":false,"given":"Andreas","family":"Diefenbach","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity Department of Microbiology Infectious Diseases and Immunology Campus Benjamin Franklin Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Berlin Institute of Health (BIH) Anna\u2010Louisa\u2010Karsch Strasse 2  Berlin Germany"},{"name":"Deutsches Rheuma\u2010Forschungszentrum Mucosal and Developmental Immunology  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Ardolino","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Cancer Therapeutics Program  Ottawa Ontario Canada"},{"name":"Centre for Infection, Immunity and Inflammation University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology, and Immunology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Santoni","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"},{"name":"IRCCS Neuromed  Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-512X","authenticated-orcid":false,"given":"Giuseppe","family":"Scium\u00e8","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Laboratory affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-3262"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.017"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2020.08.009"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.08.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.11.016"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20122097"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.030"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131560"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00076-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3094"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.03.024"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2035"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1787"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303469"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302765"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01659"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500689"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.06.016"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747294"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.043"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47605"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3368"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0425-y"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01252"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12705"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3800"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3809"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11813"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.017"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.019"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005641107"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.052"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0430-1"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201007405\u20105"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1953"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba4177"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02972"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847480"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201970107"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99317"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202149209","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.202149209","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202149209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T16:23:22Z","timestamp":1692980602000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.202149209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":43,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/eji.202149209"],"URL":"https:\/\/doi.org\/10.1002\/eji.202149209","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.202149209\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202149209\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,19]]},"assertion":[{"value":"2021-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}