%0 Journal Article
%A Reiß, Julian
%A Ghosh, Sujal
%A Scheid, Michael
%A Graafen, Lea
%A Scherenschlich, Nadine
%A Weinhold, Sandra
%A Raba, Katharina
%A Paulusch, Stefan
%A De Dominico, Elena
%A Pham, Thi X U
%A Beyer, Marc
%A Laws, Hans-Jürgen
%A Niehues, Tim
%A Borkhardt, Arndt
%A Uhrberg, Markus
%A Bennstein, Sabrina B
%T A human NK cell progenitor that originates in the thymus and generates KIR+NKG2A- NK cells.
%J Science advances
%V 11
%N 32
%@ 2375-2548
%C Washington, DC [u.a.]
%I Assoc.
%M DZNE-2025-00943
%P eadv9650
%D 2025
%X KIR+NKG2A- 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+NKG2A- 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+ double-negative thymocytes. Both generated comparable NK cell frequencies, while only thyILC1s could be efficiently differentiated into KIR+NKG2A- NK cells. Last, patients with FOXN1 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+NKG2A- NK cells.
%K Humans
%K Killer Cells, Natural: metabolism
%K Killer Cells, Natural: cytology
%K Killer Cells, Natural: immunology
%K Thymus Gland: cytology
%K Thymus Gland: immunology
%K Thymus Gland: metabolism
%K NK Cell Lectin-Like Receptor Subfamily C: metabolism
%K Cell Differentiation
%K Receptors, KIR: metabolism
%K NK Cell Lectin-Like Receptor Subfamily C (NLM Chemicals)
%K Receptors, KIR (NLM Chemicals)
%K KLRC1 protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40779632
%2 pmc:PMC12333686
%R 10.1126/sciadv.adv9650
%U https://pub.dzne.de/record/280288