Membrane-bound IL-15 stimulation on peripheral blood natural kiler progenitors leads to the generation of an adherent subset co-expressing dendritic cells and natural kiler functional markers

Simone Negrini, Massimo Giuliani, Deniz Durali, Salem Chouaib, Bruno Azzarone

Research output: Contribution to journalArticlepeer-review

Abstract

Human peripheral blood natural killer progenitors represent a flexible, heterogeneous population whose phenotype and function are controlled by their membrane-bound IL-15. Indeed, reciprocal membrane-bond IL-15 trans-presentation commits these cells into NK differentiation, while membrane-bound IL-15 stimulation with its soluble ligand (sIL-15Rα) triggers a reverse signal (pERK1/2 and pFAK) that modifies the developmental program of at least two subsets of PB-NKPs. This treatment generates: i) the expansion of an immature NK subset growing in suspension; ii) the appearance of an unprecedented adherent non-proliferative subset with a dendritic morphology co-expressing marker, cytokines and functions typical of myeloid dendritic cells (CD1a+/BDCA1+/IL-12+) and NK cells (CD3-/NKp46+/ CD56+/IFNγ +). The generation of these putative NK/DCs is associated to the rapid inhibition of negative regulators of myelopoiesis (the transcription factors STAT6 and GATA-3) followed by the transient upregulation of inducers of myeloid development, such as the transcription factors (PU.1, GATA-1) and the anti-apoptotic molecule (MCL-1).

Original languageEnglish
Pages (from-to)762-766
Number of pages5
JournalHaematologica
Volume96
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • Membranebound il-15
  • Nk progenitors
  • Peripheral blood

ASJC Scopus subject areas

  • Hematology

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