{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:56:43Z","timestamp":1773734203157,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korean government","award":["RS-2022-NR070846"],"award-info":[{"award-number":["RS-2022-NR070846"]}]},{"name":"Korean government","award":["RS-2025-24534285"],"award-info":[{"award-number":["RS-2025-24534285"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural killer (NK) cells, key effectors of innate immunity, are classically categorized into CD56dim and CD56bright subsets in humans. While murine NK cell heterogeneity has become increasingly recognized, the classification of mature NK cell subsets remains incompletely defined. Here, we comprehensively characterized CD127+ NK cells in mice and identified them as a distinct, mature subset, developing independently of the thymus and interleukin (IL)-15 signaling. Flow cytometric analyses revealed that CD127+ NK cells are broadly distributed across lymphoid and non-lymphoid tissues\u2014including in C57BL\/6 wild-type and athymic Foxn1\u2212\/\u2212 mice\u2014and exhibit a surface phenotype distinct from CD127\u2212 NK and thymus-derived CD127+ NK cells. Functional assays demonstrated that CD127+ NK cells produce interferon-\u03b3 and exert cytotoxic activity, despite expressing markers typically associated with immature NK cells. CD127+ NK cells were absent in IL-7R\u03b1\u2212\/\u2212 mice but present in IL-15\u2212\/\u2212 and IL-15R\u03b1\u2212\/\u2212 mice, indicating a selective dependence on IL-7 signaling. IL-7 promoted their proliferation and activation both in vitro and in vivo. These findings revise current models of NK cell development by identifying a novel, IL-7-responsive, IL-15-independent, thymus-independent, and functionally competent CD127+ NK cell subset that is phenotypically distinct from helper-like innate lymphoid cells (ILCs). This study provides a framework for future investigations on NK cell heterogeneity, tissue specialization, and cytokine-mediated regulation.<\/jats:p>","DOI":"10.3390\/ijms27062667","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:10:43Z","timestamp":1773655843000},"page":"2667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD127+ Natural Killer Cells Represent a Distinct, Interleukin-15-Independent and Thymus-Independent Subset in Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6458-6225","authenticated-orcid":false,"given":"Yuna","family":"Kim","sequence":"first","affiliation":[{"name":"School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6198-5742","authenticated-orcid":false,"given":"Seon-Yeong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Jin","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1980-1871","authenticated-orcid":false,"given":"Lata","family":"Rajbongshi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Rin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seongwon","family":"Joo","sequence":"additional","affiliation":[{"name":"School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seongheum","family":"Park","sequence":"additional","affiliation":[{"name":"School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sae-Ock","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6693-0003","authenticated-orcid":false,"given":"Byoung-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Biomedical Convergence Engineering, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6828-401X","authenticated-orcid":false,"given":"Dongjun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine, Pusan National University College of Medicine, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6449-0761","authenticated-orcid":false,"given":"Sik","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"},{"name":"Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/35095564","article-title":"Natural killer cells, viruses and cancer","volume":"1","author":"Cerwenka","year":"2001","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/1521-4141(200205)32:5<1205::AID-IMMU1205>3.0.CO;2-Y","article-title":"Human natural killer cells: Their origin, receptors and function","volume":"32","author":"Moretta","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vojdani, A., Koksoy, S., Vojdani, E., Engelman, M., Benzvi, C., and Lerner, A. (2024). Natural killer cells and cytotoxic T cells: Complementary partners against microorganisms and cancer. Microorganisms, 12.","DOI":"10.3390\/microorganisms12010230"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41392-024-02005-w","article-title":"Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization","volume":"9","author":"Chen","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.coi.2008.03.005","article-title":"Line of attack: NK cell specificity and integration of signals","volume":"20","author":"Bryceson","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/embor.2009.203","article-title":"Hidden talents of natural killers: NK cells in innate and adaptive immunity","volume":"10","author":"Cooper","year":"2009","journal-title":"EMBO Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0952-7915(99)80023-5","article-title":"Development and tolerance of natural killer cells","volume":"11","author":"Raulet","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"ref_8","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","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_9","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","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.molimm.2004.07.017","article-title":"Peripheral NK cell phenotypes: Multiple changing of faces of an adapting, developing cell","volume":"42","author":"Perussia","year":"2005","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.coi.2005.01.005","article-title":"Distinguishing features of developing natural killer cells","volume":"17","author":"Vosshenrich","year":"2005","journal-title":"Curr. Opin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev.immunol.24.021605.090700","article-title":"Natural killer cell developmental pathways: A question of balance","volume":"24","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Luetke-Eversloh, M., Killig, M., and Romagnani, C. (2013). Signatures of human NK cell development and terminal differentiation. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00499"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.it.2013.07.005","article-title":"Location and cellular stages of natural killer cell development","volume":"34","author":"Yu","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_15","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","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0092-8674(00)80453-5","article-title":"Identification of clonogenic common lymphoid progenitors in mouse bone marrow","volume":"91","author":"Kondo","year":"1997","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1084\/jem.190.11.1617","article-title":"Commitment of common T\/Natural killer (NK) progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay","volume":"190","author":"Ikawa","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1182\/blood.V99.2.463","article-title":"Identification of the earliest prethymic bipotent T\/NK progenitor in murine fetal liver","volume":"99","author":"Douagi","year":"2002","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yang, P., Chen, X., Wen, H., Yu, M., Yu, H., Wang, L., Gong, L., and Zhao, L. (2025). In vitro differentiation of common lymphoid progenitor cells into B cell using stromal cell free culture system. BMC Immunol., 26.","DOI":"10.1186\/s12865-025-00694-8"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, X., and Zhao, X.Y. (2021). Transcription factors associated with IL-15 cytokine signaling during NK cell development. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.610789"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5164","DOI":"10.1073\/pnas.091537598","article-title":"Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2","volume":"98","author":"Ikawa","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.immunol.17.1.19","article-title":"The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens","volume":"17","author":"Waldmann","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/1074-7613(95)90047-0","article-title":"Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain","volume":"2","author":"Cao","year":"1995","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1073\/pnas.92.2.377","article-title":"Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain","volume":"92","author":"DiSanto","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","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":"ref_26","doi-asserted-by":"crossref","first-page":"669","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":"ref_27","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.4049\/jimmunol.162.5.2761","article-title":"Dissecting NK cell development using a novel alymphoid mouse model: Investigating the role of the c-abl proto-oncogene in murine NK cell differentiation","volume":"162","author":"Colucci","year":"1999","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"771","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":"ref_29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0167-5699(99)01581-9","article-title":"The emerging role of IL-15 in NK-cell development","volume":"21","author":"Liu","year":"2000","journal-title":"Immunol. Today"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1084\/jem.20021836","article-title":"Interleukin (IL)-15R\u03b1-deficient natural killer cells survive in normal but not IL-15R\u03b1-deficient mice","volume":"197","author":"Koka","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.4110\/in.2025.25.e17","article-title":"Cytokines in focus: IL-2 and IL-15 in NK adoptive cell cancer immunotherapy","volume":"25","author":"Marr","year":"2025","journal-title":"Immune Netw."},{"key":"ref_32","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","year":"2011","journal-title":"Blood"},{"key":"ref_33","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","year":"2011","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Goh, W., and Huntington, N.D. (2017). Regulation of murine natural killer cell development. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00130"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bi, J., and Wang, X. (2020). Molecular regulation of NK cell maturation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01945"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, D., and Malarkannan, S. (2020). Transcriptional regulation of natural killer cell development and functions. Cancers, 12.","DOI":"10.3390\/cancers12061591"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1182\/blood-2010-07-298901","article-title":"Unique progenitors in mouse lymph node develop into CD127+ NK cells: Thymus-dependent and thymus-independent pathways","volume":"117","author":"Luther","year":"2011","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1084\/jem.20150809","article-title":"Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection","volume":"212","author":"Goossens","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41590-024-01865-2","article-title":"Distinct developmental pathways generate functionally distinct populations of natural killer cells","volume":"25","author":"Ding","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41423-024-01164-8","article-title":"Eomesodermin spatiotemporally orchestrates the early and late stages of NK cell development by targeting KLF2 and T-bet, respectively","volume":"21","author":"He","year":"2024","journal-title":"Cell. Mol. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/s41590-024-01861-6","article-title":"Eomes expression identifies the early bone marrow precursor to classical NK cells","volume":"25","author":"Liang","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e77294","DOI":"10.7554\/eLife.77294","article-title":"The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function","volume":"11","author":"Li","year":"2022","journal-title":"eLife"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/imr.13332","article-title":"Tissue-resident memory NK cells: Homing in on local effectors and regulators","volume":"323","author":"Schuster","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1182\/blood.V79.12.3239.bloodjournal79123239","article-title":"CD16- CD56+ natural killer cells after bone marrow transplantation","volume":"79","author":"Jacobs","year":"1992","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"400","DOI":"10.4049\/jimmunol.161.1.400","article-title":"Differential expression and function of L-selectin on CD56bright and CD56dim natural killer cell subsets","volume":"161","author":"Frey","year":"1998","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S1471-4906(01)02060-9","article-title":"The biology of human natural killer-cell subsets","volume":"22","author":"Cooper","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1600-065X.2006.00454.x","article-title":"Functional subsets of mouse natural killer cells","volume":"214","author":"Hayakawa","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1517","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":"ref_49","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1093\/intimm\/dxn022","article-title":"Application of CD27 as a marker for distinguishing human NK cell subsets","volume":"20","author":"Silva","year":"2008","journal-title":"Int. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1177\/1753425916658111","article-title":"CD27 natural killer cell subsets play different roles during the pre-onset stage of experimental autoimmune encephalomyelitis","volume":"22","author":"Gao","year":"2016","journal-title":"Innate Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/ni1395","article-title":"A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127","volume":"7","author":"Vosshenrich","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.cell.2018.07.017","article-title":"Innate Lymphoid Cells: 10 Years On","volume":"174","author":"Vivier","year":"2018","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.coi.2020.08.009","article-title":"Natural killers or ILC1s? That is the question","volume":"68","author":"Seillet","year":"2021","journal-title":"Curr. Opin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-3-031-85340-1_2","article-title":"Innate Lymphoid Cells","volume":"1476","author":"Joseph","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kuo, I.C., Brassard, J., Zandstra, P.W., and McNagny, K.M. (2025). Innate lymphoid cells in the spotlight: From biomarkers to blueprint for innovative immunotherapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1655730"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41590-025-02414-1","article-title":"The development of innate lymphoid cells","volume":"27","author":"Das","year":"2026","journal-title":"Nat. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4416","DOI":"10.1182\/blood-2004-08-3156","article-title":"A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules","volume":"105","author":"Fernandez","year":"2005","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nature03847","article-title":"Licensing of natural killer cells by host major histocompatibility complex class I molecules","volume":"436","author":"Kim","year":"2005","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.immuni.2006.06.013","article-title":"Human NK cell education by inhibitory receptors for MHC class I","volume":"25","author":"Anfossi","year":"2006","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1182\/blood-2006-07-036228","article-title":"A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature","volume":"110","author":"Cooley","year":"2007","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.4049\/jimmunol.165.9.4985","article-title":"Differentiation of murine NK cells into distinct subsets based on variable expression of the IL-12R beta 2 subunit","volume":"165","author":"Chakir","year":"2000","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nm1352","article-title":"Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity","volume":"12","author":"Chan","year":"2006","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1600-065X.2006.00461.x","article-title":"Bone marrow versus thymic pathways of natural killer cell development","volume":"214","author":"Vosshenrich","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nm1356","article-title":"A novel dendritic cell subset involved in tumor immunosurveillance","volume":"12","author":"Taieb","year":"2006","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1084\/jem.20071451","article-title":"CD11cloB220+ interferon-producing killer dendritic cells are activated natural killer cells","volume":"204","author":"Vosshenrich","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1084\/jem.20070991","article-title":"Development and function of murine B220+CD11c+NK1.1+ cells identify them as a subset of NK cells","volume":"204","author":"Blasius","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1084\/jem.20071351","article-title":"Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells","volume":"204","author":"Caminschi","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nri2154","article-title":"Developmental pathways that generate natural-killer-cell diversity in mice and humans","volume":"7","author":"Huntington","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1182\/blood-2002-09-2876","article-title":"CD56 bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: A potential new link between adaptive and innate immunity","volume":"101","author":"Fehniger","year":"2003","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.immuni.2005.01.013","article-title":"A human D34(+) subset resides in lymph nodes and differentiates into CD56bright natural killer cells","volume":"22","author":"Freud","year":"2005","journal-title":"Immunity"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1182\/blood-2001-12-0293","article-title":"In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells","volume":"100","author":"Cooper","year":"2002","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1084\/jem.20021847","article-title":"In vivo survival and homeostatic proliferation of natural killer cells","volume":"197","author":"Prlic","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1084\/jem.20030725","article-title":"IL-7 promotes the transition of CD4 effectors to persistent memory cells","volume":"198","author":"Li","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1084\/jem.178.1.257","article-title":"Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody","volume":"178","author":"Grabstein","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1084\/jem.184.1.289","article-title":"Interleukin-7 receptor alpha is essential for the development of gamma delta + T cells, but not natural killer cells","volume":"184","author":"He","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.4049\/jimmunol.157.6.2366","article-title":"Inhibition of gamma Delta T cell development and early thymocyte maturation in IL-7 -\/- mice","volume":"157","author":"Moore","year":"1996","journal-title":"J. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1084\/jem.180.5.1955","article-title":"Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice","volume":"180","author":"Peschon","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1084\/jem.181.4.1519","article-title":"Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine","volume":"181","author":"Vieira","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wu, Y., Tian, Z., and Wei, H. (2017). Developmental and functional control of natural killer cells by cytokines. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00930"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1073\/pnas.050588297","article-title":"In vivo natural killer cell activities revealed by natural killer cell-deficient mice","volume":"97","author":"Kim","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.jaci.2007.05.022","article-title":"Chronic lymphocytosis of functionally immature natural killer cells","volume":"120","author":"French","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1182\/blood-2005-04-1493","article-title":"Arrested natural killer cell development associated with transgene insertion into the Atf2 locus","volume":"107","author":"Kim","year":"2006","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6330","DOI":"10.1073\/pnas.96.11.6330","article-title":"The natural killer gene complex genetic locus Chok encodes Ly-49D, a target recognition receptor that activates natural killing","volume":"96","author":"Idris","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1084\/jem.182.2.293","article-title":"Cloning and functional characteristics of murine large granular lymphocyte-1: A member of the Ly-49 gene family (Ly-49G2)","volume":"182","author":"Mason","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1084\/jem.191.8.1341","article-title":"Nonstochastic coexpression of activation receptors on murine natural killer cells","volume":"191","author":"Smith","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/ni954","article-title":"Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors","volume":"4","author":"Iizuka","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.4049\/jimmunol.156.7.2436","article-title":"LPS induces NK1.1+ alpha beta T cells with potent cytotoxicity in the liver of mice via production of IL-12 from Kupffer cells","volume":"156","author":"Takahashi","year":"1996","journal-title":"J. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2667\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:37:33Z","timestamp":1773725853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,14]]},"references-count":87,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062667"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062667","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,14]]}}}