{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:31:30Z","timestamp":1792215090754,"version":"4.4.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells\n                    <jats:italic>via<\/jats:italic>\n                    gene regulation of IL-15R\u03b2 (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.854312","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T02:42:26Z","timestamp":1654742546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["FOXO1 and FOXO3 Cooperatively Regulate Innate Lymphoid Cell Development"],"prefix":"10.3389","volume":"13","author":[{"given":"Thuy T.","family":"Luu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas N\u00f8rskov","family":"S\u00f8ndergaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Pe\u00f1a-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Kharazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Krstic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Meinke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Schmied","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Frengen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaser","family":"Heshmati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Kierczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Bouderlique","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnika Kathleen","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Gustafsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict J.","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnane","family":"Achour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Kutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petter","family":"H\u00f6glund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"M\u00e5nsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadir","family":"Kadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.it.2010.10.005","article-title":"Foxo: In Command of T Lymphocyte Homeostasis and Tolerance","volume":"32","author":"Ouyang","year":"2011","journal-title":"Trends Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1319","article-title":"Daf-16: An HNF-3\/Forkhead Family Member That Can Function to Double the Life-Span of Caenorhabditis Elegans","volume":"278","author":"Lin","year":"1997","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.02.005","article-title":"FoxO Transcription Factors in the Maintenance of Cellular Homeostasis During Aging","volume":"20","author":"Salih","year":"2008","journal-title":"Curr Opin Cell Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.24.9138-9148.2000","article-title":"Forkhead Transcription Factor FKHR-L1 Modulates Cytokine-Dependent Transcriptional Regulation of P27(KIP1)","volume":"20","author":"Dijkers","year":"2000","journal-title":"Mol Cell Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/35099574","article-title":"Forkhead Transcription Factors Contribute to Execution of the Mitotic Programme in Mammals","volume":"413","author":"Alvarez","year":"2001","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.5.2181-2189.2004","article-title":"Control of Cyclin G2 mRNA Expression by Forkhead Transcription Factors: Novel Mechanism for Cell Cycle Control by Phosphoinositide 3-Kinase and Forkhead","volume":"24","author":"Martinez-Gac","year":"2004","journal-title":"Mol Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1689","article-title":"Foxo1 Links Homing and Survival of Naive T Cells by Regulating L-Selectin, CCR7 and Interleukin 7 Receptor","volume":"10","author":"Kerdiles","year":"2009","journal-title":"Nat Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.02.003","article-title":"An Essential Role of the Forkhead-Box Transcription Factor Foxo1 in Control of T Cell Homeostasis and Tolerance","volume":"30","author":"Ouyang","year":"2009","journal-title":"Immunity"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.015","article-title":"Transcription Factor Foxo1 Represses T-Bet-Mediated Effector Functions and Promotes Memory CD8(+) T Cell Differentiation","volume":"36","author":"Rao","year":"2012","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200639","article-title":"Intrinsic Role of FoxO3a in the Development of CD8+ T Cell Memory","volume":"190","author":"Tzelepis","year":"2013","journal-title":"J Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100004","article-title":"Transcription Factors Foxo3a and Foxo1 Couple the E3 Ligase Cbl-B to the Induction of Foxp3 Expression in Induced Regulatory T Cells","volume":"207","author":"Harada","year":"2010","journal-title":"J Exp Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.immuni.2010.12.002","article-title":"Foxo Transcription Factors Control Regulatory T Cell Development and Function","volume":"33","author":"Kerdiles","year":"2010","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1884","article-title":"Foxo Proteins Cooperatively Control the Differentiation of Foxp3+ Regulatory T Cells","volume":"11","author":"Ouyang","year":"2010","journal-title":"Nat Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nature11581","article-title":"Novel Foxo1-Dependent Transcriptional Programs Control T(reg) Cell Function","volume":"491","author":"Ouyang","year":"2012","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1667","article-title":"Distinct Functions for the Transcription Factor Foxo1 at Various Stages of B Cell Differentiation","volume":"9","author":"Dengler","year":"2008","journal-title":"Nat Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211427109","article-title":"Positive Intergenic Feedback Circuitry, Involving EBF1 and FOXO1, Orchestrates B-Cell Fate","volume":"109","author":"Mansson","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161263","article-title":"The Transcription Factor Foxo1 Controls Germinal Center B Cell Proliferation in Response to T Cell Help","volume":"214","author":"Inoue","year":"2017","journal-title":"J Exp Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12330","article-title":"Selection, Tuning, and Adaptation in Mouse NK Cell Education","volume":"267","author":"Kadri","year":"2015","journal-title":"Immunol Rev"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nri2835","article-title":"Current Perspectives of Natural Killer Cell Education by MHC Class I Molecules","volume":"10","author":"Hoglund","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/82_2015_485","article-title":"Dynamic Regulation of NK Cell Responsiveness","volume":"395","author":"Kadri","year":"2016","journal-title":"Curr Top Microbiol Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00930","article-title":"Developmental and Functional Control of Natural Killer Cells by Cytokines","volume":"8","author":"Wu","year":"2017","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","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","year":"2011","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/j.immuni.2019.02.022","article-title":"An Id2(RFP)-Reporter Mouse Redefines Innate Lymphoid Cell Precursor Potentials","volume":"50","author":"Xu","year":"2019","journal-title":"Immunity"},{"key":"B25","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nature13047","article-title":"A Committed Precursor to Innate Lymphoid Cells","volume":"508","author":"Constantinides","year":"2014","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.immuni.2019.05.002","article-title":"Polychromic Reporter Mice Reveal Unappreciated Innate Lymphoid Cell Progenitor Heterogeneity and Elusive ILC3 Progenitors in Bone Marrow","volume":"51","author":"Walker","year":"2019","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1423244112","article-title":"PLZF Expression Maps the Early Stages of ILC1 Lineage Development","volume":"112","author":"Constantinides","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00130","article-title":"Regulation of Murine Natural Killer Cell Development","volume":"8","author":"Goh","year":"2017","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132398","article-title":"The Transcription Factor E4bp4\/Nfil3 Controls Commitment to the NK Lineage and Directly Regulates Eomes and Id2 Expression","volume":"211","author":"Male","year":"2014","journal-title":"J Exp Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.04.006","article-title":"Gene Deregulation and Chronic Activation in Natural Killer Cells Deficient in the Transcription Factor ETS1","volume":"36","author":"Ramirez","year":"2012","journal-title":"Immunity"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.06.071","article-title":"The Transcription Factor Tcf1 Contributes to Normal NK Cell Development and Function by Limiting the Expression of Granzymes","volume":"20","author":"Jeevan-Raj","year":"2017","journal-title":"Cell Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.02.006","article-title":"Transcription Factor Foxo1 Is a Negative Regulator of Natural Killer Cell Maturation and Function","volume":"42","author":"Deng","year":"2015","journal-title":"Immunity"},{"key":"B33","doi-asserted-by":"publisher","first-page":"11023","DOI":"10.1038\/ncomms11023","article-title":"FoxO1-Mediated Autophagy Is Required for NK Cell Development and Innate Immunity","volume":"7","author":"Wang","year":"2016","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01016","article-title":"Hematopoietic-Specific Deletion of Foxo1 Promotes NK Cell Specification and Proliferation","volume":"10","author":"Huang","year":"2019","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1836009","article-title":"Ly6d Marks the Earliest Stage of B-Cell Specification and Identifies the Branchpoint Between B-Cell and T-Cell Development","volume":"23","author":"Inlay","year":"2009","journal-title":"Genes Dev"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-236398","article-title":"Single-Cell Analysis of the Common Lymphoid Progenitor Compartment Reveals Functional and Molecular Heterogeneity","volume":"115","author":"Mansson","year":"2010","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-017-0369-7","article-title":"Transcriptional Regulators Dictate Innate Lymphoid Cell Fates","volume":"8","author":"Zhong","year":"2017","journal-title":"Protein Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1084\/jem.185.3.499","article-title":"Abnormal Development of Intestinal Intraepithelial Lymphocytes and Peripheral Natural Killer Cells in Mice Lacking the IL-2 Receptor Beta Chain","volume":"185","author":"Suzuki","year":"1997","journal-title":"J Exp Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00355","article-title":"IL-15-PI3K-AKT-mTOR: A Critical Pathway in the Life Journey of Natural Killer Cells","volume":"6","author":"Ali","year":"2015","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141703","article-title":"PDK1 Orchestrates Early NK Cell Development Through Induction of E4BP4 Expression and Maintenance of IL-15 Responsiveness","volume":"212","author":"Yang","year":"2015","journal-title":"J Exp Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02590","article-title":"JAK\/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation","volume":"10","author":"Gotthardt","year":"2019","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12479","article-title":"Characterization of the Direct Targets of FOXO Transcription Factors Throughout Evolution","volume":"15","author":"Webb","year":"2016","journal-title":"Aging Cell"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00312","article-title":"Age-Dependent Changes in Transcription Factor FOXO Targeting in Female Drosophila","volume":"10","author":"Birnbaum","year":"2019","journal-title":"Front Genet"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.03.010","article-title":"Akt, FoxO and Regulation of Apoptosis","volume":"1813","author":"Zhang","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2006.08.015","article-title":"Mitogen-Activated Protein Kinases, Erk and P38, Phosphorylate and Regulate Foxo1","volume":"19","author":"Asada","year":"2007","journal-title":"Cell Signal"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/immu.200310005","article-title":"Transgenic Mice With Hematopoietic and Lymphoid Specific Expression of Cre","volume":"33","author":"de Boer","year":"2003","journal-title":"Eur J Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.029","article-title":"FoxOs are Lineage-Restricted Redundant Tumor Suppressors and Regulate Endothelial Cell Homeostasis","volume":"128","author":"Paik","year":"2007","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086336","article-title":"Suppression of Ovarian Follicle Activation in Mice by the Transcription Factor Foxo3a","volume":"301","author":"Castrillon","year":"2003","journal-title":"Science"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1517","article-title":"CD27 Dissects Mature NK Cells Into Two Subsets With Distinct Responsiveness and Migratory Capacity","volume":"176","author":"Hayakawa","year":"2006","journal-title":"J Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1002\/eji.201948233","article-title":"IL-15 and CD155 Expression Regulate LAT Expression in Murine DNAM1 (+) NK Cells, Enhancing Their Effectors Functions","volume":"50","author":"Luu","year":"2019","journal-title":"Eur J Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12574","article-title":"The Abl-1 Kinase Is Dispensable for NK Cell Inhibitory Signalling and Is Not Involved in Murine NK Cell Education","volume":"86","author":"Ganesan","year":"2017","journal-title":"Scand J Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.005","article-title":"Development, Differentiation, and Diversity of Innate Lymphoid Cells","volume":"41","author":"Diefenbach","year":"2014","journal-title":"Immunity"},{"key":"B53","doi-asserted-by":"publisher","first-page":"37996","DOI":"10.1038\/srep37996","article-title":"Independent Control of Natural Killer Cell Responsiveness and Homeostasis at Steady-State by CD11c+ Dendritic Cells","volume":"6","author":"Luu","year":"2016","journal-title":"Sci Rep"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5527","article-title":"NKG2D Receptors Induced by IL-15 Costimulate CD28-Negative Effector CTL in the Tissue Microenvironment","volume":"167","author":"Roberts","year":"2001","journal-title":"J Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/ni1524","article-title":"NKG2D Signaling is Coupled to the Interleukin 15 Receptor Signaling Pathway","volume":"8","author":"Horng","year":"2007","journal-title":"Nat Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.1098","article-title":"CXCL9 and CXCL10 Expression Are Critical for Control of Genital Herpes Simplex Virus Type 2 Infection Through Mobilization of HSV-Specific CTL and NK Cells to the Nervous System","volume":"180","author":"Thapa","year":"2008","journal-title":"J Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.4.869","article-title":"Induction of Interferon Gamma Production by Natural Killer Cell Stimulatory Factor: Characterization of the Responder Cells and Synergy With Other Inducers","volume":"173","author":"Chan","year":"1991","journal-title":"J Exp Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(98)80163-5","article-title":"Regulation of Interferon-Gamma Production by IL-12 and IL-18","volume":"10","author":"Okamura","year":"1998","journal-title":"Curr Opin Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.12.007","article-title":"The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15","volume":"44","author":"Delconte","year":"2016","journal-title":"Immunity"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80638-X","article-title":"The Ets-1 Transcription Factor Is Required for the Development of Natural Killer Cells in Mice","volume":"9","author":"Barton","year":"1998","journal-title":"Immunity"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3768","article-title":"Genomic Footprinting","volume":"13","author":"Vierstra","year":"2016","journal-title":"Nat Methods"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105136","article-title":"The ENCODE (ENCyclopedia Of DNA Elements) Project","volume":"306","author":"Consortium","year":"2004","journal-title":"Science"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e1001046","DOI":"10.1371\/journal.pbio.1001046","article-title":"A User\u2019s Guide to the Encyclopedia of DNA Elements (ENCODE)","volume":"9","year":"2011","journal-title":"PLoS Biol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3094","article-title":"Transcriptional Programs Define Molecular Characteristics of Innate Lymphoid Cell Classes and Subsets","volume":"16","author":"Robinette","year":"2015","journal-title":"Nat Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00167","article-title":"NK Cell-Based Immune Checkpoint Inhibition","volume":"11","author":"Khan","year":"2020","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.07.013","article-title":"The Transcription Factor Foxo1 Controls Central-Memory CD8+ T Cell Responses to Infection","volume":"39","author":"Kim","year":"2013","journal-title":"Immunity"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.10.003","article-title":"Hematopoietic Fingerprints: An Expression Database of Stem Cells and Their Progeny","volume":"1","author":"Chambers","year":"2007","journal-title":"Cell Stem Cell"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.2174\/138945011796150316","article-title":"Regulation of Foxo-Dependent Transcription by Post-Translational Modifications","volume":"12","author":"Boccitto","year":"2011","journal-title":"Curr Drug Targets"},{"key":"B69","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.stem.2016.11.007","article-title":"A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland","volume":"20","author":"Cai","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1210\/me.2014-1164","article-title":"Control of Hepatic Gluconeogenesis by the Promyelocytic Leukemia Zinc Finger Protein","volume":"28","author":"Chen","year":"2014","journal-title":"Mol Endocrinol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08798","article-title":"Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat","volume":"69","author":"Liska","year":"2017","journal-title":"Hypertension"},{"key":"B72","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1038\/s41467-021-25758-2","article-title":"Sequential Actions of EOMES and T-BET Promote Stepwise Maturation of Natural Killer Cells","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat Commun"},{"key":"B73","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.celrep.2015.03.006","article-title":"DNAM-1 Expression Marks an Alternative Program of NK Cell Maturation","volume":"11","author":"Martinet","year":"2015","journal-title":"Cell Rep"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.5.771","article-title":"Reversible Defects in Natural Killer and Memory CD8 T Cell Lineages in Interleukin 15-Deficient Mice","volume":"191","author":"Kennedy","year":"2000","journal-title":"J Exp Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80664-0","article-title":"IL-15 Receptor Maintains Lymphoid Homeostasis by Supporting Lymphocyte Homing and Proliferation","volume":"9","author":"Lodolce","year":"1998","journal-title":"Immunity"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3392","article-title":"IL-15 Is an Essential Mediator of Peripheral NK-Cell Homeostasis","volume":"101","author":"Ranson","year":"2003","journal-title":"Blood"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.3.1213","article-title":"Roles for Common Cytokine Receptor Gamma-Chain-Dependent Cytokines in the Generation, Differentiation, and Maturation of NK Cell Precursors and Peripheral NK Cells In Vivo","volume":"174","author":"Vosshenrich","year":"2005","journal-title":"J Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00455","article-title":"The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification","volume":"10","author":"Bouderlique","year":"2019","journal-title":"Front Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616","article-title":"Edger: A Bioconductor Package for Differential Expression Analysis of Digital Gene Expression Data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-808063","article-title":"Active Enhancer and Chromatin Accessibility Landscapes Chart the Regulatory Network of Primary Multiple Myeloma","volume":"131","author":"Jin","year":"2018","journal-title":"Blood"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.016","article-title":"DNase Footprint Signatures Are Dictated by Factor Dynamics and DNA Sequence","volume":"56","author":"Sung","year":"2014","journal-title":"Mol Cell"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.040","article-title":"Circuitry and Dynamics of Human Transcription Factor Regulatory Networks","volume":"150","author":"Neph","year":"2012","journal-title":"Cell"},{"key":"B83","unstructured":"One-Way ANOVA Followed by Dunnett\u2019s Multiple Comparisons Test was Performed Using GraphPad Prism Version 6.00 for Mac OS X"},{"key":"B84","unstructured":"R: A Language and Environment for Statistical Computing R Foundation for Statistical Computing2008"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.854312\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T02:42:31Z","timestamp":1654742551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.854312\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,9]]},"references-count":84,"alternative-id":["10.3389\/fimmu.2022.854312"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.854312","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.01.13.426512","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,9]]},"article-number":"854312"}}