{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:38:35Z","timestamp":1780915115657,"version":"3.54.1"},"reference-count":95,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"32","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,8]]},"abstract":"<jats:p>\n            KIR\n            <jats:sup>+<\/jats:sup>\n            NKG2A\n            <jats:sup>\u2212<\/jats:sup>\n            natural killer (NK) cells have the unique ability to detect down-regulation of single HLA-I allotypes, frequently occurring in malignantly transformed and virus-infected cells. We have recently shown that circulating innate lymphoid cells 1 (cILC1s) have the potential to generate such KIR\n            <jats:sup>+<\/jats:sup>\n            NKG2A\n            <jats:sup>\u2212<\/jats:sup>\n            NK cells, but their developmental origin was unknown. Here, we demonstrate that the development of cILC1 is thymus dependent and identify a putative progenitor of cILC1s in the thymus (thyILC1). Single-cell RNA sequencing analysis revealed a close relationship of thyILC1s to CD34\n            <jats:sup>+<\/jats:sup>\n            double-negative thymocytes. Both generated comparable NK cell frequencies, while only thyILC1s could be efficiently differentiated into KIR\n            <jats:sup>+<\/jats:sup>\n            NKG2A\n            <jats:sup>\u2212<\/jats:sup>\n            NK cells. Last, patients with\n            <jats:italic toggle=\"yes\">FOXN1<\/jats:italic>\n            haploinsufficiency, showing congenital thymic hypoplasia, exhibited a profound deficiency of cILC1s but not cILC2s and cILC3s, demonstrating their specific thymus dependency. Together, the data suggest that thyILC1s are the source of a thymus-dependent NK cell differentiation pathway that promotes generation of KIR\n            <jats:sup>+<\/jats:sup>\n            NKG2A\n            <jats:sup>\u2212<\/jats:sup>\n            NK cells.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adv9650","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T17:58:46Z","timestamp":1754675926000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["A human NK cell progenitor that originates in the thymus and generates KIR\n            <sup>+<\/sup>\n            NKG2A\n            <sup>\u2212<\/sup>\n            NK cells"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2540-5736","authenticated-orcid":true,"given":"Julian","family":"Rei\u00df","sequence":"first","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, Moorenstr. 5, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5647-4262","authenticated-orcid":true,"given":"Sujal","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scheid","sequence":"additional","affiliation":[{"name":"Herzzentrum Duisburg, Evangelisches Klinikum Niederrhein, Gerrickstra\u00dfe 21, Duisburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Graafen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0361-6375","authenticated-orcid":true,"given":"Nadine","family":"Scherenschlich","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, Moorenstr. 5, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0725-4199","authenticated-orcid":true,"given":"Sandra","family":"Weinhold","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, Moorenstr. 5, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8818-4219","authenticated-orcid":true,"given":"Katharina","family":"Raba","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, Moorenstr. 5, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Paulusch","sequence":"additional","affiliation":[{"name":"PRECISE Platform for Genomics and Epigenomics at German Center for Neurodegenerative Diseases (DZNE) and University of Bonn and West German Genome Center, Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0336-8284","authenticated-orcid":true,"given":"Elena","family":"De Dominico","sequence":"additional","affiliation":[{"name":"PRECISE Platform for Genomics and Epigenomics at German Center for Neurodegenerative Diseases (DZNE) and University of Bonn and West German Genome Center, Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi X. U.","family":"Pham","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, Moorenstr. 5, D\u00fcsseldorf, Germany."},{"name":"Department of Pediatrics, Helios Klinikum Krefeld, Krefeld, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-148X","authenticated-orcid":true,"given":"Marc","family":"Beyer","sequence":"additional","affiliation":[{"name":"PRECISE Platform for Genomics and Epigenomics at German Center for Neurodegenerative Diseases (DZNE) and University of Bonn and West German Genome Center, Bonn, Germany."},{"name":"Immunogenomics &amp; Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-J\u00fcrgen","family":"Laws","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-8833","authenticated-orcid":true,"given":"Tim","family":"Niehues","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Helios Klinikum Krefeld, Krefeld, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Borkhardt","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-1987","authenticated-orcid":true,"given":"Markus","family":"Uhrberg","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, Moorenstr. 5, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0477-2748","authenticated-orcid":true,"given":"Sabrina B.","family":"Bennstein","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, Moorenstr. 5, D\u00fcsseldorf, Germany."},{"name":"Institute of Immunology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-427781"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.017"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.06.016"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2104"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.20-0300"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.021"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55232"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12478"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-015-1750-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54420-w"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80393-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1995.0009"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.9.2182.2182"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-020198"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.02.008"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018019059"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.058"},{"key":"e_1_3_2_19_2","first-page":"229","article-title":"Natural killer cells, HLA class I molecules, and marrow transplantation","volume":"3","author":"Valiante N. 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