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.
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).
UMR 1014 Inserm, Paul Brousse Hospital, Villejuif, France.
Simone
S
Negrini
Massimo
M
Giuliani
Deniz
D
Durali
Salem
S
Chouaib
Bruno
B
Azzarone
D015153:Blotting, Western; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053647:Receptors, Interleukin-15 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D019089:Stem Cell Factor / Q000494:pharmacology
D016207:Cytokines; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050990:GATA3 Transcription Factor; C508024:IL15RA protein, human; D019409:Interleukin-15; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D053647:Receptors, Interleukin-15; D050800:STAT6 Transcription Factor; D019089:Stem Cell Factor
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