Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in Fetal and Adult Tissues

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Virginie M Renoux - , Lund University (Author)
  • Alya Zriwil - , Lund University (Author)
  • Claudia Peitzsch - , Lund Stem Cell Center, Lund University (Author)
  • Jakob Michaëlsson - , Karolinska University Hospital (Author)
  • Danielle Friberg - , Karolinska University Hospital (Author)
  • Shamit Soneji - , Lund University (Author)
  • Ewa Sitnicka - , Lund University (Author)

Abstract

Natural killer (NK) cells are cytotoxic lymphocytes and play a vital role in controlling viral infections and cancer. In contrast to B and T lymphopoiesis where cellular and regulatory pathways have been extensively characterized, the cellular stages of early human NK cell commitment remain poorly understood. Here we demonstrate that a Lin(-)CD34(+)CD38(+)CD123(-)CD45RA(+)CD7(+)CD10(+)CD127(-) population represents a NK lineage-restricted progenitor (NKP) in fetal development, umbilical cord blood, and adult tissues. The newly identified NKP has robust NK cell potential both in vitro and in vivo, generates functionally cytotoxic NK cells, and lacks the ability to produce T cells, B cells, myeloid cells, and innate lymphoid-like cells (ILCs). Our findings identify an early step to human NK cell commitment and provide new insights into the human hematopoietic hierarchy.

Details

Original languageEnglish
Pages (from-to)394-407
Number of pages14
JournalImmunity
Volume43
Issue number2
Publication statusPublished - 18 Aug 2015
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84940997861
ORCID /0000-0002-5247-908X/work/142241943

Keywords

Sustainable Development Goals

Keywords

  • Adult, Antigens, CD/metabolism, Cell Differentiation, Cell Lineage, Cytotoxicity, Immunologic, Fetal Blood/cytology, Fetal Development, Fetus/cytology, Hematopoiesis/immunology, Humans, Immunity, Innate, Immunophenotyping, Killer Cells, Natural/physiology, Lymphoid Progenitor Cells/physiology