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@ARTICLE{Rei:280288,
author = {Reiß, Julian and Ghosh, Sujal and Scheid, Michael and
Graafen, Lea and Scherenschlich, Nadine and Weinhold, Sandra
and Raba, Katharina and Paulusch, Stefan and De Dominico,
Elena and Pham, Thi X U and Beyer, Marc and Laws,
Hans-Jürgen and Niehues, Tim and Borkhardt, Arndt and
Uhrberg, Markus and Bennstein, Sabrina B},
title = {{A} human {NK} cell progenitor that originates in the
thymus and generates {KIR}+{NKG}2{A}- {NK} cells.},
journal = {Science advances},
volume = {11},
number = {32},
issn = {2375-2548},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {DZNE-2025-00943},
pages = {eadv9650},
year = {2025},
abstract = {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.},
keywords = {Humans / Killer Cells, Natural: metabolism / Killer Cells,
Natural: cytology / Killer Cells, Natural: immunology /
Thymus Gland: cytology / Thymus Gland: immunology / Thymus
Gland: metabolism / NK Cell Lectin-Like Receptor Subfamily
C: metabolism / Cell Differentiation / Receptors, KIR:
metabolism / NK Cell Lectin-Like Receptor Subfamily C (NLM
Chemicals) / Receptors, KIR (NLM Chemicals) / KLRC1 protein,
human (NLM Chemicals)},
cin = {AG Schultze / PRECISE / AG Beyer},
ddc = {500},
cid = {I:(DE-2719)1013038 / I:(DE-2719)1013031 /
I:(DE-2719)1013035},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354) / 352
- Disease Mechanisms (POF4-352) / 351 - Brain Function
(POF4-351)},
pid = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-352 /
G:(DE-HGF)POF4-351},
experiment = {EXP:(DE-2719)PRECISE-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40779632},
pmc = {pmc:PMC12333686},
doi = {10.1126/sciadv.adv9650},
url = {https://pub.dzne.de/record/280288},
}