Home > Publications Database > A human NK cell progenitor that originates in the thymus and generates KIR+NKG2A- NK cells. > print

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082 _ _ |a 500
100 1 _ |a Reiß, Julian
|0 0009-0002-2540-5736
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245 _ _ |a A human NK cell progenitor that originates in the thymus and generates KIR+NKG2A- NK cells.
260 _ _ |a Washington, DC [u.a.]
|c 2025
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520 _ _ |a 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.
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650 _ 7 |a NK Cell Lectin-Like Receptor Subfamily C
|2 NLM Chemicals
650 _ 7 |a Receptors, KIR
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650 _ 7 |a KLRC1 protein, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Killer Cells, Natural: metabolism
|2 MeSH
650 _ 2 |a Killer Cells, Natural: cytology
|2 MeSH
650 _ 2 |a Killer Cells, Natural: immunology
|2 MeSH
650 _ 2 |a Thymus Gland: cytology
|2 MeSH
650 _ 2 |a Thymus Gland: immunology
|2 MeSH
650 _ 2 |a Thymus Gland: metabolism
|2 MeSH
650 _ 2 |a NK Cell Lectin-Like Receptor Subfamily C: metabolism
|2 MeSH
650 _ 2 |a Cell Differentiation
|2 MeSH
650 _ 2 |a Receptors, KIR: metabolism
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700 1 _ |a Ghosh, Sujal
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700 1 _ |a Weinhold, Sandra
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700 1 _ |a Raba, Katharina
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700 1 _ |a Paulusch, Stefan
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700 1 _ |a Beyer, Marc
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700 1 _ |a Laws, Hans-Jürgen
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700 1 _ |a Niehues, Tim
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700 1 _ |a Borkhardt, Arndt
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700 1 _ |a Uhrberg, Markus
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700 1 _ |a Bennstein, Sabrina B
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773 _ _ |a 10.1126/sciadv.adv9650
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