Potently Cytotoxic Natural Killer Cells Initially Emerge from Erythro-Myeloid Progenitors during Mammalian Development.

Autor:	Dege C; Department of Medicine, Division of Hematology, Washington University in St Louis, St. Louis, MO 63110, USA., Fegan KH; Center for Pediatric Biomedical Research and Department of Pediatrics, University of Rochester, Rochester, NY 14642, USA., Creamer JP; Department of Medicine, Division of Hematology, Washington University in St Louis, St. Louis, MO 63110, USA., Berrien-Elliott MM; Department of Medicine, Division of Oncology, Washington University in St Louis, St. Louis, MO 63110, USA., Luff SA; Department of Medicine, Division of Hematology, Washington University in St Louis, St. Louis, MO 63110, USA., Kim D; Department of Medicine, Division of Hematology, Washington University in St Louis, St. Louis, MO 63110, USA., Wagner JA; Department of Medicine, Division of Oncology, Washington University in St Louis, St. Louis, MO 63110, USA., Kingsley PD; Center for Pediatric Biomedical Research and Department of Pediatrics, University of Rochester, Rochester, NY 14642, USA., McGrath KE; Center for Pediatric Biomedical Research and Department of Pediatrics, University of Rochester, Rochester, NY 14642, USA., Fehniger TA; Department of Medicine, Division of Oncology, Washington University in St Louis, St. Louis, MO 63110, USA., Palis J; Center for Pediatric Biomedical Research and Department of Pediatrics, University of Rochester, Rochester, NY 14642, USA. Electronic address: james_palis@urmc.rochester.edu., Sturgeon CM; Department of Medicine, Division of Hematology, Washington University in St Louis, St. Louis, MO 63110, USA; Department of Developmental Biology, Washington University in St Louis, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University in St Louis, St. Louis, MO 63110, USA. Electronic address: csturgeon@wustl.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2020 Apr 20; Vol. 53 (2), pp. 229-239.e7. Date of Electronic Publication: 2020 Mar 19.
DOI:	10.1016/j.devcel.2020.02.016
Abstrakt:	Natural killer (NK) cells are a critical component of the innate immune system. However, their ontogenic origin has remained unclear. Here, we report that NK cell potential first arises from Hoxa neg/low Kit + CD41 + CD16/32 + hematopoietic-stem-cell (HSC)-independent erythro-myeloid progenitors (EMPs) present in the murine yolk sac. EMP-derived NK cells and primary fetal NK cells, unlike their adult counterparts, exhibit robust degranulation in response to stimulation. Parallel studies using human pluripotent stem cells (hPSCs) revealed that HOXA neg/low CD34 + progenitors give rise to NK cells that, similar to murine EMP-derived NK cells, harbor a potent cytotoxic degranulation bias. In contrast, hPSC-derived HOXA + CD34 + progenitors, as well as human cord blood CD34 + cells, give rise to NK cells that exhibit an attenuated degranulation response but robustly produce inflammatory cytokines. Collectively, our studies identify an extra-embryonic origin of potently cytotoxic NK cells, suggesting that ontogenic origin is a relevant factor in designing hPSC-derived adoptive immunotherapies. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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