{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:10:22Z","timestamp":1792444222038,"version":"4.5.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"16","license":[{"start":{"date-parts":[[2015,10,2]],"date-time":"2015-10-02T00:00:00Z","timestamp":1443744000000},"content-version":"vor","delay-in-days":183,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI108643"],"award-info":[{"award-number":["R01AI108643"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI038339"],"award-info":[{"award-number":["R01AI038339"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL118092"],"award-info":[{"award-number":["R01HL118092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,4,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Diverse populations of group 1 innate lymphocytes, which exert critical early cytolytic functions against virally infected cells, have recently been discovered, raising issues of lineage relationships. We used expression of the transcription factor promyelocytic leukaemia zinc finger (PLZF) to identify the developmental intermediates of innate lymphoid cells type 1 (ILC1s), a subset of innate lymphoid cells that are particularly abundant in the liver, and demonstrated that this lineage arises from a distinct precursor, but that its development partially overlaps with established classical NK stages. Using microarray analysis, we defined a set of PLZF-dependent genes that may contribute to lineage divergence between ILC1s and classical NK cells.<\/jats:p>","DOI":"10.1073\/pnas.1423244112","type":"journal-article","created":{"date-parts":[[2015,4,3]],"date-time":"2015-04-03T09:02:58Z","timestamp":1428051778000},"page":"5123-5128","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":158,"title":["PLZF expression maps the early stages of ILC1 lineage development"],"prefix":"10.1073","volume":"112","author":[{"given":"Michael G.","family":"Constantinides","sequence":"first","affiliation":[{"name":"Committee on Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Gudjonson","sequence":"additional","affiliation":[{"name":"Institute for Biophysical Dynamics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Committee on Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel E.","family":"Ishizuka","sequence":"additional","affiliation":[{"name":"Committee on Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A.","family":"Verhoef","sequence":"additional","affiliation":[{"name":"Committee on Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron R.","family":"Dinner","sequence":"additional","affiliation":[{"name":"Committee on Immunology,"},{"name":"Institute for Biophysical Dynamics, and"},{"name":"Department of Chemistry, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Bendelac","sequence":"additional","affiliation":[{"name":"Committee on Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,4,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3390\/v1030362","article-title":"The natural selection of herpesviruses and virus-specific NK cell receptors","volume":"1","author":"Sun JC","year":"2009","unstructured":"JC Sun, LL Lanier, The natural selection of herpesviruses and virus-specific NK cell receptors. Viruses 1, 362 (2009).","journal-title":"Viruses"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.immunol.22.012703.104711","article-title":"The dynamic life of natural killer cells","volume":"22","author":"Yokoyama WM","year":"2004","unstructured":"WM Yokoyama, S Kim, AR French, The dynamic life of natural killer cells. Annu Rev Immunol 22, 405\u2013429 (2004).","journal-title":"Annu Rev Immunol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.1198687","article-title":"Innate or adaptive immunity? The example of natural killer cells","volume":"331","author":"Vivier E","year":"2011","unstructured":"E Vivier, , Innate or adaptive immunity? The example of natural killer cells. Science 331, 44\u201349 (2011).","journal-title":"Science"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"e01659","DOI":"10.7554\/eLife.01659","article-title":"Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells","volume":"3","author":"Sojka DK","year":"2014","unstructured":"DK Sojka, , Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells. eLife 3, e01659 (2014).","journal-title":"eLife"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1101\/sqb.2013.78.020354","article-title":"Tissue-resident natural killer cells","volume":"78","author":"Yokoyama WM","year":"2013","unstructured":"WM Yokoyama, DK Sojka, H Peng, Z Tian, Tissue-resident natural killer cells. Cold Spring Harb Symp Quant Biol 78, 149\u2013156 (2013).","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1172\/JCI66381","article-title":"Liver-resident NK cells confer adaptive immunity in skin-contact inflammation","volume":"123","author":"Peng H","year":"2013","unstructured":"H Peng, , Liver-resident NK cells confer adaptive immunity in skin-contact inflammation. J Clin Invest 123, 1444\u20131456 (2013).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.4049\/jimmunol.1303469","article-title":"Cutting edge: Salivary gland NK cells develop independently of Nfil3 in steady-state","volume":"192","author":"Cortez VS","year":"2014","unstructured":"VS Cortez, A Fuchs, M Cella, S Gilfillan, M Colonna, Cutting edge: Salivary gland NK cells develop independently of Nfil3 in steady-state. J Immunol 192, 4487\u20134491 (2014).","journal-title":"J Immunol"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.immuni.2013.02.010","article-title":"Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-\u03b3-producing cells","volume":"38","author":"Fuchs A","year":"2013","unstructured":"A Fuchs, , Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-\u03b3-producing cells. Immunity 38, 769\u2013781 (2013).","journal-title":"Immunity"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.smim.2014.01.010","article-title":"Tissue-resident natural killer cells and their potential diversity","volume":"26","author":"Sojka DK","year":"2014","unstructured":"DK Sojka, Z Tian, WM Yokoyama, Tissue-resident natural killer cells and their potential diversity. Semin Immunol 26, 127\u2013131 (2014).","journal-title":"Semin Immunol"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.cell.2014.03.030","article-title":"Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages","volume":"157","author":"Klose CS","year":"2014","unstructured":"CS Klose, , Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157, 340\u2013356 (2014).","journal-title":"Cell"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1084\/jem.20131560","article-title":"T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow","volume":"211","author":"Daussy C","year":"2014","unstructured":"C Daussy, , T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow. J Exp Med 211, 563\u2013577 (2014).","journal-title":"J Exp Med"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1182\/blood-2004-08-3262","article-title":"TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver","volume":"105","author":"Takeda K","year":"2005","unstructured":"K Takeda, , TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood 105, 2082\u20132089 (2005).","journal-title":"Blood"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.immuni.2011.11.016","article-title":"The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation","volume":"36","author":"Gordon SM","year":"2012","unstructured":"SM Gordon, , The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. Immunity 36, 55\u201367 (2012).","journal-title":"Immunity"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.coi.2013.02.002","article-title":"Developmental programming of natural killer and innate lymphoid cells","volume":"25","author":"Vosshenrich CA","year":"2013","unstructured":"CA Vosshenrich, JP Di Santo, Developmental programming of natural killer and innate lymphoid cells. Curr Opin Immunol 25, 130\u2013138 (2013).","journal-title":"Curr Opin Immunol"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nature13047","article-title":"A committed precursor to innate lymphoid cells","volume":"508","author":"Constantinides MG","year":"2014","unstructured":"MG Constantinides, BD McDonald, PA Verhoef, A Bendelac, A committed precursor to innate lymphoid cells. Nature 508, 397\u2013401 (2014).","journal-title":"Nature"},{"key":"e_1_3_4_16_2","first-page":"3","article-title":"The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor","volume":"3","author":"Yu X","year":"2014","unstructured":"X Yu, , The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor. eLife 3, 3 (2014).","journal-title":"eLife"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/ni796","article-title":"In vivo developmental stages in murine natural killer cell maturation","volume":"3","author":"Kim S","year":"2002","unstructured":"S Kim, , In vivo developmental stages in murine natural killer cell maturation. Nat Immunol 3, 523\u2013528 (2002).","journal-title":"Nat Immunol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/1521-4141(200106)31:6<1900::AID-IMMU1900>3.0.CO;2-M","article-title":"Identification of committed NK cell progenitors in adult murine bone marrow","volume":"31","author":"Rosmaraki EE","year":"2001","unstructured":"EE Rosmaraki, , Identification of committed NK cell progenitors in adult murine bone marrow. Eur J Immunol 31, 1900\u20131909 (2001).","journal-title":"Eur J Immunol"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"5439","DOI":"10.1182\/blood-2011-04-348912","article-title":"Identification of the earliest natural killer cell-committed progenitor in murine bone marrow","volume":"118","author":"Fathman JW","year":"2011","unstructured":"JW Fathman, , Identification of the earliest natural killer cell-committed progenitor in murine bone marrow. Blood 118, 5439\u20135447 (2011).","journal-title":"Blood"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1182\/blood-2010-11-318956","article-title":"Identification of the earliest NK-cell precursor in the mouse BM","volume":"117","author":"Carotta S","year":"2011","unstructured":"S Carotta, SH Pang, SL Nutt, GT Belz, Identification of the earliest NK-cell precursor in the mouse BM. Blood 117, 5449\u20135452 (2011).","journal-title":"Blood"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.immuni.2012.06.020","article-title":"The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells","volume":"37","author":"Hoyler T","year":"2012","unstructured":"T Hoyler, , The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37, 634\u2013648 (2012).","journal-title":"Immunity"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.immuni.2014.09.005","article-title":"Development, differentiation, and diversity of innate lymphoid cells","volume":"41","author":"Diefenbach A","year":"2014","unstructured":"A Diefenbach, M Colonna, S Koyasu, Development, differentiation, and diversity of innate lymphoid cells. Immunity 41, 354\u2013365 (2014).","journal-title":"Immunity"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1146\/annurev.iy.09.040191.003335","article-title":"The immunobiology of T cells with invariant gamma delta antigen receptors","volume":"9","author":"Allison JP","year":"1991","unstructured":"JP Allison, WL Havran, The immunobiology of T cells with invariant gamma delta antigen receptors. Annu Rev Immunol 9, 679\u2013705 (1991).","journal-title":"Annu Rev Immunol"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.4049\/jimmunol.149.6.1876","article-title":"Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes","volume":"149","author":"Lanier LL","year":"1992","unstructured":"LL Lanier, C Chang, H Spits, JH Phillips, Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes. J Immunol 149, 1876\u20131880 (1992).","journal-title":"J Immunol"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nature11813","article-title":"A T-bet gradient controls the fate and function of CCR6(-)RORgammat(+) innate lymphoid cells","volume":"494","author":"Klose CS","year":"2013","unstructured":"CS Klose, , A T-bet gradient controls the fate and function of CCR6(-)RORgammat(+) innate lymphoid cells. Nature 494, 261\u2013265 (2013).","journal-title":"Nature"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ni.3078","article-title":"IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential \u2018inflammatory\u2019 type 2 innate lymphoid cells","volume":"16","author":"Huang Y","year":"2015","unstructured":"Y Huang, , IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential \u2018inflammatory\u2019 type 2 innate lymphoid cells. Nat Immunol 16, 161\u2013169 (2015).","journal-title":"Nat Immunol"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/bioinformatics\/btn224","article-title":"lumi: A pipeline for processing Illumina microarray","volume":"24","author":"Du P","year":"2008","unstructured":"P Du, WA Kibbe, SM Lin, lumi: A pipeline for processing Illumina microarray. Bioinformatics 24, 1547\u20131548 (2008).","journal-title":"Bioinformatics"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1093\/nar\/gkm1075","article-title":"Model-based variance-stabilizing transformation for Illumina microarray data","volume":"36","author":"Lin SM","year":"2008","unstructured":"SM Lin, P Du, W Huber, WA Kibbe, Model-based variance-stabilizing transformation for Illumina microarray data. Nucleic Acids Res 36, e11 (2008).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/0-387-29362-0_23","volume-title":"Bioinformatics and Computational Biology Solutions Using R and Bioconductor","author":"Smyth GK","year":"2005","unstructured":"GK Smyth, Limma: Linear models for microarray data. Bioinformatics and Computational Biology Solutions Using R and Bioconductor, eds R Gentleman, V Carey, S Dudoit, R Irizarry, W Huber (Springer, New York), pp. 397\u2013420 (2005)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1423244112","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1423244112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T01:04:37Z","timestamp":1691543077000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1423244112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,2]]},"references-count":29,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2015,4,21]]}},"alternative-id":["10.1073\/pnas.1423244112"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1423244112","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,2]]},"assertion":[{"value":"2015-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}