TY  - JOUR
AU  - Reiß, Julian
AU  - Ghosh, Sujal
AU  - Scheid, Michael
AU  - Graafen, Lea
AU  - Scherenschlich, Nadine
AU  - Weinhold, Sandra
AU  - Raba, Katharina
AU  - Paulusch, Stefan
AU  - De Dominico, Elena
AU  - Pham, Thi X U
AU  - Beyer, Marc
AU  - Laws, Hans-Jürgen
AU  - Niehues, Tim
AU  - Borkhardt, Arndt
AU  - Uhrberg, Markus
AU  - Bennstein, Sabrina B
TI  - A human NK cell progenitor that originates in the thymus and generates KIR+NKG2A- NK cells.
JO  - Science advances
VL  - 11
IS  - 32
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DZNE-2025-00943
SP  - eadv9650
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Killer Cells, Natural: metabolism
KW  - Killer Cells, Natural: cytology
KW  - Killer Cells, Natural: immunology
KW  - Thymus Gland: cytology
KW  - Thymus Gland: immunology
KW  - Thymus Gland: metabolism
KW  - NK Cell Lectin-Like Receptor Subfamily C: metabolism
KW  - Cell Differentiation
KW  - Receptors, KIR: metabolism
KW  - NK Cell Lectin-Like Receptor Subfamily C (NLM Chemicals)
KW  - Receptors, KIR (NLM Chemicals)
KW  - KLRC1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40779632
C2  - pmc:PMC12333686
DO  - DOI:10.1126/sciadv.adv9650
UR  - https://pub.dzne.de/record/280288
ER  -